Use Of Neurotrophic Factors Research Articles

The Use of Neurotrophic Factors as a Promising Strategy for the Treatment of Neurodegenerative Diseases (Review).

The review considers the use of exogenous neurotrophic factors in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and others. This group of diseases is associated with the death of neurons and dysfunction of the nervous tissue. Currently, there is no effective therapy for neurodegenerative diseases, and their treatment remains a serious problem of modern medicine. A promising strategy is the use of exogenous neurotrophic factors. Targeted delivery of these factors to the nervous tissue can improve survival of neurons during the development of neurodegenerative processes and ensure neuroplasticity. There are methods of direct injection of neurotrophic factors into the nervous tissue, delivery using viral vectors, as well as the use of gene cell products. The effectiveness of these approaches has been studied in numerous experimental works and in a number of clinical trials. Further research in this area could provide the basis for the creation of an alternative treatment for neurodegenerative diseases.

IGF-1 gene therapy prevents spatial memory deficits and modulates dopaminergic neurodegeneration and inflammation in a parkinsonism model

Cognitive impairment in Parkinson’s disease is considered an indicator of the prodromal stages of this condition, occurring prior to the onset of classic and pathognomonic motor symptoms. Among other factors, neuroinflammation is increasingly recognized as a potential mediator of this neurodegenerative process, and glial cells are directly involved. However, the use of neurotrophic factors is associated with neuroprotection and cognitive improvements. Among all those factors, insulin-like growth factor 1 (IGF-1) has attracted considerable attention. In this study, we aimed to investigate the effect of IGF-1 gene therapy in an early animal model of 6-hydroxidopamine (6-OHDA)- induced parkinsonism.For this purpose, we employed male Wistar rats. The animals were first divided into two groups according to the bilateral injection into de Caudate Putamen unit (CPu):(a) VEH group (vehicle solution) and (b) 6-OHDA group (neurotoxic solution). After that, the animals in each group were divided, according to the bilateral injection into the dorsal hippocampus, in a control group (who received a control virus RAd-DSRed) and an experimental group (who received a therapeutic virus (RAd-IGF1). After three weeks of exposure to 6-OHDA, our study showed that IGF-1 gene therapy improved cognitive deficits related to short-term and spatial working memory, it also increased expression levels of tyrosine hydroxylase in the CPu. In addition, the therapy resulted in significant changes in several parameters (area, perimeter, roundness, ramification, and skeleton ́s analyses) related to microglia and astrocyte phenotypes, particularly in the CPu and dorsal hippocampal areas.Our data support the use of IGF-1 as a therapeutic molecule for future gene transfer interventions, that will contribute to a better understanding of the mechanisms correlating cognitive function and inflammatory process.

INFLUENCE OF FIBROBLAST GROWTH FACTOR-2 ON THE ACTIVATION OF MOUSE HIPPOCAMPAL MICROGLIA IN A LIPOPOLYSACCHARIDE-INDUCED NEUROINFLAMMATION MODEL IN VITRO

Introduction. Activation of the pro-inflammatory phenotype of microglia may be one of the causes of chronic neuroinflammation and, as a result, can lead to pathological conditions of the brain. The use of neurotrophic factors, such as FGF2, may become one of the promising methods for correcting neurodegenerative diseases, but the question of the influence of this factor on microglia activation is still open. The purpose of this work was to study the effect of FGF2 on the activation of mouse hippocampal microglia in an in vitro model of neuroinflammation induced by lipopolysaccharide. Material and methods. The study was carried out on a culture of primary mixed glial cells of the mouse hippocampus. To quantify, area, and morphological changes in microglial cells in response to the effects of LPS and FGF2, immunocytochemical analysis was performed for markers of astrocytes (GFAP) and microglia (Iba-1). Analysis of the expression level of IL-1β, IL-6, IL-10, TNF-α was carried out by quantitative PCR. Results. In response to LPS exposure, there was an increase in the percentage of Iba-1+ cells, their surface area, changes in morphological characteristics, together with an increase in the level of expression of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and anti-inflammatory cytokine IL-10 both within 6, so 12 hours of exposition. The addition of FGF2 led to a decrease in the percentage of Iba-1+ cells in culture and a decrease in the surface area of microglia. A decrease in the relative level of expression of IL-1β and IL-6 was noted in the groups where LPS and FGF2 were added, while the expression of TNF-α did not change. With an increase in cultivation time up to 12 hours, an increased expression of IL-10 was detected in this group. Conclusion. Stimulation with LPS promotes the transition of microglia from a resting to an activated pro-inflammatory phenotype, as evidenced by increased proliferative activity of Iba-1+ cells in combination with an increase in the level of expression of pro-inflammatory cytokines. Inhibition of two of the three pro-inflammatory cytokines (IL-1β and IL-6) and a significant increase in the level of IL-10 in cell culture suggests an anti-inflammatory effect of FGF2.

Therapeutic potential of neurotrophic factors in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia among the elderly population. AD is accompanied with the dysregulation of specific neurotrophic factors (NTFs) and their receptors, which plays a critical role in neuronal degeneration. NTFs are small proteins with therapeutic potential for human neurodegenerative diseases. These growth factors are categorized into four families: neurotrophins, neurokines, the glial cell line-derived NTF family of ligands, and the newly discovered cerebral dopamine NTF/mesencephalic astrocyte-derived NTF family. NTFs are capable of preventing cell death in degenerative conditions and can increase the neuronal growth and function in these disorders. Nevertheless, the adverse side effects of NTFs delivery and poor diffusion of these factors in the brain restrict the efficacy of NTFs therapy in clinical situations. In this review, we focus on the current advances in the use of NTFs to treat AD and summarize previous experimental and clinical studies for supporting the protective and therapeutic effects of these factors. Based on reports, NTFs are considered as new and promising candidates for treating AD and AD-associated cognitive impairment.

A Novel Small Molecule Neurotrophin-3 Analogue Promotes Inner Ear Neurite Outgrowth and Synaptogenesis In vitro.

Sensorineural hearing loss is irreversible and is associated with the loss of spiral ganglion neurons (SGNs) and sensory hair cells within the inner ear. Improving spiral ganglion neuron (SGN) survival, neurite outgrowth, and synaptogenesis could lead to significant gains for hearing-impaired patients. There has therefore been intense interest in the use of neurotrophic factors in the inner ear to promote both survival of SGNs and re-wiring of sensory hair cells by surviving SGNs. Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) represent the primary neurotrophins in the inner ear during development and throughout adulthood, and have demonstrated potential for SGN survival and neurite outgrowth. We have pioneered a hybrid molecule approach to maximize SGN stimulation in vivo, in which small molecule analogues of neurotrophins are linked to bisphosphonates, which in turn bind to cochlear bone. We have previously shown that a small molecule BDNF analogue coupled to risedronate binds to bone matrix and promotes SGN neurite outgrowth and synaptogenesis in vitro. Because NT-3 has been shown in a variety of contexts to have a greater regenerative capacity in the cochlea than BDNF, we sought to develop a similar approach for NT-3. 1Aa is a small molecule analogue of NT-3 that has been shown to activate cells through TrkC, the NT-3 receptor, although its activity on SGNs has not previously been described. Herein we describe the design and synthesis of 1Aa and a covalent conjugate of 1Aa with risedronate, Ris-1Aa. We demonstrate that both 1Aa and Ris-1Aa stimulate neurite outgrowth in SGN cultures at a significantly higher level compared to controls. Ris-1Aa maintained its neurotrophic activity when bound to hydroxyapatite, the primary mineral component of bone. Both 1Aa and Ris-1Aa promote significant synaptic regeneration in cochlear explant cultures, and both 1Aa and Ris-1Aa appear to act at least partly through TrkC. Our results provide the first evidence that a small molecule analogue of NT-3 can stimulate SGNs and promote regeneration of synapses between SGNs and inner hair cells. Our findings support the promise of hydroxyapatite-targeting bisphosphonate conjugation as a novel strategy to deliver neurotrophic agents to SGNs encased within cochlear bone.

Facial Nerve Repair: Bioengineering Approaches in Preclinical Models.

Injury to the facial nerve can occur after different etiologies and range from simple transection of the branches to varying degrees of segmental loss. Management depends on the extent of injury and options include primary repair for simple transections and using autografts, allografts, or conduits for larger gaps. Tissue engineering plays an important role to create artificial materials that are able to mimic the nerve itself without extra morbidity in the patients. The use of neurotrophic factors or stem cells inside the conduits or around the repair site is being increasingly studied to enhance neural recovery to a greater extent. Preclinical studies remain the hallmark for development of these novel approaches and translation into clinical practice. This review will focus on preclinical models of repair after facial nerve injury to help researchers establish an appropriate model to quantify recovery and analyze functional outcomes. Different bioengineered materials, including conduits and nerve grafts, will be discussed based on the experimental animals that were used and the defects introduced. Future directions to extend the applications of processed nerve allografts, bioengineered conduits, and cues inside the conduits to induce neural recovery after facial nerve injury will be highlighted. Impact statement Recovery after facial nerve injury is a complex process, which involves different management options such as primary repair or the use of nerve grafts or conduits. Various tissue-engineered approaches are increasingly studied on preclinical models with limited, but promising, translation to the clinical setting. Herein, preclinical models focusing on different recovery methods after facial nerve injury are comprehensively reviewed based on the experimental animals used. The review provides key insights into current developments and future directions on this highly relevant topic to help researchers further expand the field of tissue engineering and facial nerve recovery.

Neurotrophic Factors in Glaucoma and Innovative Delivery Systems

Glaucoma is a neurodegenerative disease and a worldwide leading cause of irreversible vision loss. In the last decades, high efforts have been made to develop novel treatments effective in inducing protection and/or recovery of neural function in glaucoma, including neurotrophic factors (NTFs). These approaches have shown encouraging data in preclinical setting; however, the challenge of sustained, targeted delivery to the retina and optic nerve still prevents the clinical translation. In this paper, the authors review and discuss the most recent advances for the use of NTFs treatment in glaucoma, including intraocular delivery. Novel strategies in drug and gene delivery technology for NTFs are proving effective in promoting long-term retinal ganglion cells (RGCs) survival and related functional improvements. Results of experimental and clinical studies evaluating the efficacy and safety of biodegradable slow-release NTF-loaded microparticle devices, encapsulated NTF-secreting cells implants, mimetic ligands for NTF receptors, and viral and non-viral NTF gene vehicles are discussed. NTFs are able to prevent and even reverse apoptotic ganglion cell death. Nevertheless, neuroprotection in glaucoma remains an open issue due to the unmet need of sustained delivery to the posterior segment of the eye. The recent advances in intraocular delivery systems pave the way for possible future use of NTFs in clinical practice for the treatment of glaucoma.

Impact of neurotrophic factors combination therapy on retinitis pigmentosa

ObjectiveWe aimed to determine the location of neurotrophic receptors tropomyosin receptor kinase (Trk)B, TrkC, and ciliary neurotrophic factor receptor (CNTFR)α in the retina of retinal degeneration (rd) mice and to explore the dynamic changes of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X-protein (Bax), and microtubule-associated protein light chain 3 (LC3) expression and ultrastructure in the retina of rd mice intravitreally injected with neurotrophic factors.MethodsRd mice aged 2 and 3 weeks post-natally (PN) received intravitreal injections of neurotrophic factors. Two weeks later, their retinas were harvested for the detection of Bax, Bcl-2, and LC3 mRNA and protein expression.ResultsTrkB and TrkC expression levels were lower at 3 weeks PN compared with 0, 1, and 2 weeks PN, but CNTFRα expression was still detected in certain layers. The three receptors were expressed in different retinal layers at the same timepoint. Bax expression was downregulated in, rhBDNF + rhCNTF, rhBDNF + rhNT-3, groups 2 weeks after intravitreal injection; Bcl-2 expression was upregulated in the rhBDNF + rhCNTF + rhNT-3 group at PN-4w; and LC3 expression was upregulated in rhBDNF + rhCNTF + rhNT-3 groups.ConclusionsThe combined use of neurotrophic factors had a more significant effect on Bax, Bcl-2, and LC3 expression than the same factors used alone.

MEMBRANE-RECEPTOR COMPLEX DYSFUNCTION AS A NEW TARGET FOR THE NEUROTROPHIC THERAPY OF ISCHEMIC STROKE

The aim of the study was the β-adrenergic activity of peripheral blood erythrocyte membranes in the acute period of ischemic stroke (IS). Peripheral blood erythrocytes are the most informative biological tissue for studying many pathogenetic mechanisms, and the work of their membrane-receptor complex (MRC) can very well reflect the functional state of the whole organism, one of the most important criteria for assessing is the adrenergic activity of cytoplasmic membranes in the pathogenesis of IS. This study solves the problem of the finding of the features of changes in the adrenoceptors system in the acute period of IS in the dynamics of the treatment of humans cryopreserved cord blood serum (CCBS). The main scientific results: the obtained results indicate a reduced ability of adrenoceptors (ARs) on erythrocyte membranes to bind blockers due to the desensitisation effect, which is observed from the 1st day of the disease. In the onset of IS, there is a significant increase in the values of β-adrenergic activity of membranes (β-ARM) of erythrocytes in 2.4 times compared with the control. Maximum levels of the indicator (42.43±3.64 CU) are observed in patients with initially severe disease, which indicates significant stress of the sympathoadrenal system (SAS) in these patients. On the 10th day of the disease, there was a decrease in β-ARM relative to the values obtained during hospitalisation. Still, comparing the value of the indicator on the 10th day of IS in both groups, there was an apparent, more significant decrease in β-ARM in the 2nd group of patients, which additionally received CCBS. The use of CCBS contributes to a more pronounced degree of recovery in neurological functions (6.9%) and faster stabilisation of the structure of MRCs in erythrocytes in the form of reducing the values of β-ARM to 16.61±2.86 CU (p<0.05). The area of practical use of the research results: the results of the study can be used to diagnose and treat of the IS. An innovative technological product: A comprehensive approach to assess the β-ARM of peripheral blood erythrocytes in patients with IS by determining the degree of changes in osmotic resistance of erythrocytes (ORE) under the action of adrenergic drugs (AD) is informative and can be used to diagnose of IS. The use of neurotrophic factors is a potentially new method of treating this pathology. Scope of application of the innovative technological product: in the clinical practice of neurological departments for the treatment of patients with strokes

Mutation-Independent Therapies for Retinal Diseases: Focus on Gene-Based Approaches.

Gene therapy is proving to be an effective approach to treat or prevent ocular diseases ensuring a targeted, stable, and regulated introduction of exogenous genetic material with therapeutic action. Retinal diseases can be broadly categorized into two groups, namely monogenic and complex (multifactorial) forms. The high genetic heterogeneity of monogenic forms represents a significant limitation to the application of gene-specific therapeutic strategies for a significant fraction of patients. Therefore, mutation-independent therapeutic strategies, acting on common pathways that underly retinal damage, are gaining interest as complementary/alternative approaches for retinal diseases. This review will provide an overview of mutation-independent strategies that rely on the modulation in the retina of key genes regulating such crucial degenerative pathways. In particular, we will describe how gene-based approaches explore the use of neurotrophic factors, microRNAs (miRNAs), genome editing and optogenetics in order to restore/prolong visual function in both outer and inner retinal diseases. We predict that the exploitation of gene delivery procedures applied to mutation/gene independent approaches may provide the answer to the unmet therapeutic need of a large fraction of patients with genetically heterogeneous and complex retinal diseases.

On the Right Track to Treat Movement Disorders: Promising Therapeutic Approaches for Parkinson's and Huntington's Disease.

Movement disorders are neurological conditions in which patients manifest a diverse range of movement impairments. Distinct structures within the basal ganglia of the brain, an area involved in movement regulation, are differentially affected for every disease. Among the most studied movement disorder conditions are Parkinson’s (PD) and Huntington’s disease (HD), in which the deregulation of the movement circuitry due to the loss of specific neuronal populations in basal ganglia is the underlying cause of motor symptoms. These symptoms are due to the loss principally of dopaminergic neurons of the substantia nigra (SN) par compacta and the GABAergic neurons of the striatum in PD and HD, respectively. Although these diseases were described in the 19th century, no effective treatment can slow down, reverse, or stop disease progression. Available pharmacological therapies have been focused on preventing or alleviating motor symptoms to improve the quality of life of patients, but these drugs are not able to mitigate the progressive neurodegeneration. Currently, considerable therapeutic advances have been achieved seeking a more efficacious and durable therapeutic effect. Here, we will focus on the new advances of several therapeutic approaches for PD and HD, starting with the available pharmacological treatments to alleviate the motor symptoms in both diseases. Then, we describe therapeutic strategies that aim to restore specific neuronal populations or their activity. Among the discussed strategies, the use of Neurotrophic factors (NTFs) and genetic approaches to prevent the neuronal loss in these diseases will be described. We will highlight strategies that have been evaluated in both Parkinson’s and Huntington’s patients, and also the ones with strong preclinical evidence. These current therapeutic techniques represent the most promising tools for the safe treatment of both diseases, specifically those aimed to avoid neuronal loss during disease progression.

Target-Derived Neurotrophic Factor Deprivation Puts Retinal Ganglion Cells on Death Row: Cold Hard Evidence and Caveats.

Glaucoma and other optic neuropathies are characterized by axonal transport deficits. Axonal cargo travels back and forth between the soma and the axon terminus, a mechanism ensuring homeostasis and the viability of a neuron. An example of vital molecules in the axonal cargo are neurotrophic factors (NTFs). Hindered retrograde transport can cause a scarcity of those factors in the retina, which in turn can tilt the fate of retinal ganglion cells (RGCs) towards apoptosis. This postulation is one of the most widely recognized theories to explain RGC death in the disease progression of glaucoma and is known as the NTF deprivation theory. For several decades, research has been focused on the use of NTFs as a novel neuroprotective glaucoma treatment. Until now, results in animal models have been promising, but translation to the clinic has been highly disappointing. Are we lacking important knowledge to lever NTF therapies towards the therapeutic armamentarium? Or did we get the wrong end of the stick regarding the NTF deprivation theory? In this review, we will tackle the existing evidence and caveats advocating for and against the target-derived NTF deprivation theory in glaucoma, whilst digging into associated therapy efforts.

BDNF-overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro.

The use of neurotrophic factors as therapeutic agents for neurodegenerative diseases is considered as an approach aimed at restoring and maintaining neuronal function in the peripheral and central nervous system. Since the neuroprotective effect is depending on chronic delivery of the neurotrophic factors a sustained application, e.g., via cell‐based delivery is necessary. Human mesenchymal stem cells (hMSCs) were lentivirally modified to overexpress brain‐derived neurotrophic factor (BDNF) and to express fluorescent marker genes for easy visualization. Since genetically modified cells should be site‐specifically retained (e.g., by encapsulation) in the patients to avoid adverse effects the cells were additionally differentiated to chondrocytes to hypothetically improve their vitality and survival in a delivery matrix. Different polycations for lentiviral transduction were investigated for their efficiency. The success of differentiation was determined by analysis of chondrocyte marker genes and the neuroprotective effect of BDNF‐overexpressing cells was exemplarily investigated on neurons of the peripheral auditory system. The genetically modified hMSCs overexpressed BDNF from under 1 to 125 ng ml−1 day−1 depending on the donor and transfection method. Using protamine sulfate the transfection efficacy was superior compared to the use of polybrene. The BDNF secreted by the MSCs was significantly neuroprotective in comparison to the relevant controls even though the produced mean concentrations were lower than the effective concentrations for recombinant industrially produced proteins described in literature. The presented system of BDNF‐overexpressing hMSCs is neuroprotective and is therefore considered as a promising method for sustained delivery of proteins in therapeutically relevant amounts to degenerating neuronal structures.

Therapeutic potential of conditioned medium derived from oligodendrocytes cultured in a self-assembling peptide nanoscaffold in experimental autoimmune encephalomyelitis

The use of neurotrophic factors is considered to be a novel therapeutic approach for restoring and/or maintaining neurological function in neurodegenerative disorders, such as multiple sclerosis (MS). Various studies have shown that conditioned medium produced by oligodendrocyte (OL-CM) contain a variety of neurotrophic factors. Here, we investigated the restorative effects of OL-CM, collected from oligodendrocytes cultured in a self-assembling peptide hydrogels scaffold (PuraMatrix), in experimental autoimmune encephalomyelitis (EAE) mouse model. Neural stem/progenitor cells, isolated from the embryonic mouse brain, were cultured and differentiated into oligodendrocyte. Cell viability and proliferation of oligodendrocytes were assessed by live/dead and MTT assays. Motor functions, myelination, cell infiltration, gliosis, and inflammatory process were assessed in EAE mice after intracranial injection of OL-CM at different concentrations. Application of OL-CM improved clinical score and neurological function in EAE mice and reduced the inflammatory cell infiltration and demyelination. Furthermore, administration of OL-CM reduced the expression of pro-inflammatory cytokines and suppressed the activation of NLRP3-inflammasome complex in EAE mice. These data suggest the potential therapeutic effect of OL-CM for MS treatment.

Clinical case study of Kearns–Sayre syndrome: diagnosis, methods of treatment

The article outlines the current knowledge of the etiology, pathogenesis, clinical features and diagnostic criteria of one of the forms of mitochondrial encephalomyopathy – the Kearns–Sayre syndrome. The observation of a patient with an incomplete case of the Kearns–Sayre syndrome is presented. The complexity of diagnosis and the range of differential diagnostic search as well as approaches to treatment with the use of neurotrophic factors are widely discussed in the research.

Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound

BackgroundThe use of neurotrophic factors to treat Alzheimer’s disease (AD) is hindered by their blood–brain barrier impermeability, short half-life, and severe side effects. Peptide 021 (P021) is a neurotrophic/neurogenic tetra-peptide that was derived from the most active region of the ciliary neurotrophic factor (CNTF) by epitope mapping. Admantylated glycine was added to its C-terminal to increase its blood–brain barrier permeability and decrease its degradation by exopeptidases to make it druggable. Here, we report on the preventive effect of P021 in 3 × Tg-AD, a transgenic mouse model of AD.MethodsP021 was administered in the diet at 3 months, i.e., 6–9 months before any overt amyloid beta (Aβ) or tau pathology, and during the period of synaptic compensation, and was continued until 21 months in 3 × Tg-AD mice. The 3 × Tg-AD mice and wild-type (WT) mice were treated identically but with a vehicle-only diet serving as controls. The effects of P021 on neurogenesis, dendritic and synaptic markers, and cognitive performance were investigated.ResultsWe found that P021 treatment was able to rescue dendritic and synaptic deficits, boost neurogenesis, and reverse cognitive impairment in 3 × Tg-AD mice.ConclusionsAvailability of appropriate neurotrophic support during the period of synaptic compensation can prevent synaptic deficit and cognitive impairment, and P021 is a promising neurotrophic compound for this purpose.

Clinical Effect of Leuprolide Acetate, an Agonist of GnRH, on Sensitive and Motor Function in a Patient With Chronic Spinal Cord Injury

The spinal cord is the major conduct through which sensory and motor signals pass between brain and body. Spinal cord injury (SCI) results in a disruption of these pathways and dramatic functional losses. There are different experimental approaches to counteracting the effects of SCI, such as the use of neurotrophic factors. It has been demonstrated that GnRH and its agonist leuprolide acetate (LA) have neurotrophic properties in SCI experimental model animals. Here, we report our findings from a patient suffering chronic SCI, who had undergone treatment with LA therapy. Treatment consisted of intramuscular injection of LA each month during 12 months. An important improvement in sensitive and motor functions was seen in the patient after treatment with LA. Further research is necessary to elucidate the mechanism of action of LA in SCI patients. J Neurol Res. 2016;6(5-6):111-113 doi: https://doi.org/10.14740/jnr403w

Protection of cultured dopamine neurons from MPP(+) requires a combination of neurotrophic factors.

Parkinson's disease is a progressive neurodegenerative disorder, caused in part by the loss of dopamine (DA) neurons in the substantia nigra (SN). Neurotrophic factors have been shown to increase the basal survival of DA neurons invitro, as well as to protect the neurons from some toxins under certain invitro conditions and in animal models. Although these factors have often been tested individually, they have rarely been studied in combinations. We therefore examined the effect of such combinations after acute exposure to the toxin 1-methyl-4-phenylpyridinium (MPP(+) ) using dissociated postnatal rat midbrain cultures isolated from SN and ventral tegmental area (VTA). We found that significant loss of DA neurons in the SN occurred with an LC50 of between 1 and 10μm, whereas the LC50 of DA neurons from the VTA was approximately 1000-fold higher. We did not observe neuroprotection against MPP(+) by individual exposure to glial cell-line derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF), transforming growth factor beta (TGFβ), basic fibroblast growth factor (FGF-2) or growth/differentiation factor 5 (GDF5) at concentrations of 100 or 500ng/mL. Combinations of two, three or four neurotrophic factors were also ineffective. However, when the SN cultures were exposed to a combination of all five neurotrophic factors, each at a concentration of 100ng/mL, we observed a 30% increase in DA neuron survival in the presence of 10 and 500μm MPP(+) . These results may be relevant to the use of neurotrophic factors as therapeutic treatments for Parkinson's disease.

Clinical Effect of Leuprolide Acetate, an Agonist of GnRH, on Sensitive and Motor Function in a Patient With Chronic Spinal Cord Injury

The spinal cord is the major conduct through which sensory and motor signals pass between brain and body. Spinal cord injury (SCI) results in a disruption of these pathways and dramatic functional losses. There are different experimental approaches to counteracting the effects of SCI, such as the use of neurotrophic factors. It has been demonstrated that GnRH and its agonist leuprolide acetate (LA) have neurotrophic properties in SCI experimental model animals. Here, we report our findings from a patient suffering chronic SCI, who had undergone treatment with LA therapy. Treatment consisted of intramuscular injection of LA each month during 12 months. An important improvement in sensitive and motor functions was seen in the patient after treatment with LA. Further research is necessary to elucidate the mechanism of action of LA in SCI patients. J Neurol Res. 2016;6(5-6):111-113 doi: https://doi.org/10.14740/jnr403w

More Evidence That Neurturin Does Not Address the Motor Symptoms of Parkinson Disease

There has been surging interest in the use of neurotrophic factors for the treatment of Parkinson disease. In a double-blind industry-funded trial, researchers assessed the effects of bilateral injections of the neurotrophic factor neurturin into both the substantia nigra and putamen regions of the brain. An adeno-associated virus type 2 (AAV2) vector was used to deliver neurturin. Fifty-one patients with advanced Parkinson disease were randomized to active treatment or sham …