Nervous Cells Research Articles

Exogenous Amyloid Fibrils Can Cause Significant Upregulation of Neurodegenerative Disease Proteins.

Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are associated with the formation of amyloid fibrils. In familial cases, the mutant causative genes accentuate disease progression through overexpression or misfolding of amyloidogenic proteins. Besides, considerable amyloidosis cases arise from external factors, but their origin and mechanisms are not yet fully understood. Herein, we found that amyloid fibrils generated from egg and milk proteins, in addition to their nutritional effects to intestinal cells, can selectively reduce the viability of nervous cells as well as pancreatic islet cells. In contrast, soy protein amyloid fibrils lacked cytotoxicity to the aforementioned cells. This protein source and cell type-dependent cytotoxicity are demonstrated to be associated with the significant upregulation of amyloidogenic proteins. The finding was also confirmed by the vein injection of beta-lactoglobulin fibrils to mice, exhibiting the pronounced upregulations of amyloid beta1-42 (Aβ1-42) and islet amyloid polypeptide in vivo. The study therefore provides insight into the health implications of exogenous amyloid fibrils.

Synthesis of chlorotoxin functionalized metallic nanoparticles and their in vitro evaluation of cytotoxic effects in nervous system cancer cell lines

The treatment of glioblastoma (GB) and neuroblastoma (NB) remains a challenge, as current chemotherapies are plagued with systemic toxicity, drug resistance, and inadequate blood–brain barrier (BBB) penetration. Therefore, novel therapeutic strategies with high specificity and the capacity to bypass the BBB are required. Chlorotoxin (CTX) selectively targets gliomas and neuroectodermal tumors, hence the use of CTX-targeted nanoparticles (NPs) represents a promising therapeutic approach for nervous system (NS) cancers. Bimetallic NPs composed of two metals such as gold-platinum NPs (AuPtNPs) exhibit enhanced anticancer properties compared to single-metal NPs, however their application in studying NS tumors has been relatively limited. CTX-functionalized monometallic gold NPs (CTX-AuNPs) and bimetallic gold-platinum NPs (CTX-AuPtNPs) were synthesized in this study. The NPs were characterized by Ultraviolet-Visible Spectroscopy (UV–vis), Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) and Fourier Transform Infra-Red Spectroscopy (FTIR). Cytotoxicity of NPs was investigated in cancer (U87 and SH-SY5Y) and non-cancer (KMST-6) cells using the water-soluble tetrazolium (WST)-1 assay. The CTX-AuNPs and CTX-AuPtNPs had a core size of ∼5 nm. The CTX-AuPtNPs showed significant anticancer activity in U87 cells possibly due to the synergistic effects of combined metals. Findings obtained from this study demonstrated that CTX can be used to target NS cancers and that bimetallic NPs could be effective in their treatment. More studies are required to investigate the mechanisms of NPs toxicity, and further explore the hyperthermia treatment of NS cancer using the CTX-AuPtNPs.

Impact of Enteric Nervous Cells on Irritable Bowel Syndrome: Potential Treatment Options.

Irritable bowel syndrome (IBS) is a condition that significantly impacts the lifestyle, health, and habits of numerous individuals worldwide. Its diagnosis and classification are based on the Rome criteria, updated periodically to reflect new research findings in this field. IBS can be classified into different types based on symptoms, each with distinct treatment approaches and some differences in their pathophysiology. The exact pathological background of IBS remains unclear, with many aspects still unknown. Recent research developments suggest that disorders in the brain-gut-microbiota axis are key contributors to the symptoms and severity of IBS. The central nervous system (CNS) interacts bidirectionally with intestinal processes within the lumen and the intestinal wall, with the autonomic nervous system, particularly the vagus nerve, playing an important role. However, the enteric nervous system (ENS) is also crucial in the pathophysiological pathway of IBS. The apeline-corticotropin-releasing factor (CRF)-toll-like receptor 4 (TLR4) signaling route via enteric glia and serotonin production in enteroendocrine cells at the enteric barrier are among the most well-understood new findings that affect IBS through the ENS. Additionally, the microbiota regulates neuronal signals, modifying enteric function by altering the number of enteric bacteria and other mechanisms. Given the limited therapeutic options currently available, it is essential to identify new treatment targets, with the brain-gut axis, particularly the enteric nervous system, being a promising focus. This study aims to delineate the molecular mechanisms that induce IBS and to suggest potential targets for future research and treatment of this potentially debilitating disease.

Third ventricle teratoma with malignant transformation

Intracranial germ cell tumors(GCTs) are rare and heterogeneous group of primary brain tumors, mainly affecting pediatric population and young adults. The current understanding of the etiology of intracranial GCTs and their optimal management strategies remain controversial. Treatment plans differ depending on the subtype GCT and may vary among physicians and institutions. Central nervous system non-germinomatous germ cell tumor (NGGCT) usually requires surgical resection with histological verification, chemotherapy, and radiation. The extent of surgical resection is an important prognostic factor alongside the etiology and genetics of NGGCT. This article presents a rare clinical case of a rapidly growing teratoma located in the posterior part of third ventricle of a 17-year-old male presenting with symptoms of intracranial hypertension. Surgical total resection was preceded by endoscopic third ventriculostomy. Immunohistochemistry revealed the presence of embryonal carcinoma and immature teratoma cells turning the tumor into mixed type NGGCT with unfavorable prognosis. Despite the complete resection of the tumor and the timely initiation of adjuvant therapy, a rapid progression of the disease with subsequent unfavorable outcome was observed 3.6 months after the surgical treatment.

Parkinson’s Disease and the faecal microbiota transplantation. Review of current knowledge

Introduction and Purpose. Parkinson’s Disease (PD) is a chronic neurodegenerative disorder caused by dopamine deficiency due to neuronal degeneration, leading to motor and non-motor symptoms. Gastrointestinal symptoms are common and often precede motor symptoms. There is increasing evidence that imbalanced gut microbiota may influence the gut-brain axis and contribute to motor and non-motor PD symptoms. Fecal microbiota transplantation (FMT) may have the potential to restore gut flora and improve PD symptoms. The study aims to explore the current knowledge on the impact of FMT on PD symptoms, acknowledging existing reviews and highlighting new studies not yet reviewed. Understanding the underlying causes of PD could lead to better treatment, diagnostics, and prevention.State of knowledge. PD patients suffer from specific gut dysbiosis which leads to imbalance in the produced pro- and anti-inflammatory substances in the intestinal lumen resulting in aggreviation of α-synuclein in gut nervous cells which may hypothetically transfer via vagal nerve to CNS causing PD. In animal research FMT showed promising results in alleviating PD symptoms. Case reports showed reduction of both motor and non-motor dysfunctions, especially in constipation. DuPont et al. showed improvements in constipation, motor deficits, overall Parkinson’s symptoms, and some non-motor disorders. Cheng et al. showed improvements in MDS-UPDRS, scores of GI tract symptoms scales, PD-related autonomic symptoms and the stool frequency. Bruggeman et al. showed better MDS-UPDRS part 3 scores and better colon transit, but no significant differencies in any other tested domains. Conclusions. As there is yet no standarized protocol for FMT, all of the past research used different techniques and showed slightly different outcomes, but all have shown that FMT have some positive effects on PD symptoms.

Dissecting glial scar formation by spatial point pattern and topological data analysis

Glial scar formation represents a fundamental response to central nervous system (CNS) injuries. It is mainly characterized by a well-defined spatial rearrangement of reactive astrocytes and microglia. The mechanisms underlying glial scar formation have been extensively studied, yet quantitative descriptors of the spatial arrangement of reactive glial cells remain limited. Here, we present a novel approach using point pattern analysis (PPA) and topological data analysis (TDA) to quantify spatial patterns of reactive glial cells after experimental ischemic stroke in mice. We provide open and reproducible tools using R and Julia to quantify spatial intensity, cell covariance and conditional distribution, cell-to-cell interactions, and short/long-scale arrangement, which collectively disentangle the arrangement patterns of the glial scar. This approach unravels a substantial divergence in the distribution of GFAP+ and IBA1+ cells after injury that conventional analysis methods cannot fully characterize. PPA and TDA are valuable tools for studying the complex spatial arrangement of reactive glia and other nervous cells following CNS injuries and have potential applications for evaluating glial-targeted restorative therapies.

Microglial modulation as a therapeutic strategy in Alzheimer's disease: Focus on microglial preconditioning approaches.

Alzheimer's disease (AD) is a progressive disease that causes an impairment of learning and memory. Despite the highly complex pathogenesis of AD, amyloid beta (Aβ) deposition and neurofibrillary tangles (NFTs) formation are the main hallmarks of AD. Neuroinflammation also has a crucial role in the development of AD. As the central nervous system's innate immune cells, microglial cells are activated in AD and induce inflammation by producing pro-inflammatory mediators. However, microglial activation is not always deleterious. M2-activated microglial cells are considered anti-inflammatory cells, which develop neuroprotection. Various approaches are proposed for managing AD, yet no effective therapy is available for this disorder. Considering the potential protective role of M2 microglia in neurodegenerative disorders and the improvement of these disorders by preconditioning approaches, it can be suggested that preconditioning of microglial cells may be beneficial for managing AD progression. Therefore, this study review microglial preconditioning approaches for preventing and improving AD.

The structure of the Cryptocotyle lingua miracidium (Digenea: Opisthorchiidae)

In the course of Digenea evolution the transitions to a passive strategy of infection of the first intermediate host occurred multiple times. In these cases, miracidia – ciliated larvae – relinquished their role as active seekers for a suitable snail host and began relying on the chance of being accidently ingested by it. The structural changes resulting from these transitions are diverse, but the majority of them are reductive. In this study we present our ultrastructural survey on the opisthorchioid Cryptocotyle lingua miracidium. The transition to passivity led to extensive reduction in almost all somatic elements of the larva: only four epithelial plates cover its body; just a single nervous cell, a single protonephridium and a single longitudinally-oriented muscle cell have been found in this miracidium. Several undifferentiated cells comprise the germinal material of the larva. The greatest part of its body is occupied by three glandular elements. The position of these glands is consistent within Opisthorchioidea and strikingly corresponds to that of some of the optically studied miracidia of Plagiorchioidea. This similarity is suspicious, because the C. lingua larva appeared to differ vastly from other ultrastructurally described passive miracidia. Here we create a basis for the future comparison of the miracidia of Opisthorchioidea and Plagiorchioidea, expecting the ultrastructural data on the latter to be published someday.

Acute toxicity of chemotherapy in central nervous system germ cell tumour patients according to age.

SIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed. CRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide-ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide-ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs. 296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95%CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI. Adult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity.

The cytoplasmic tail of myelin protein zero induces morphological changes in lipid membranes

The major myelin protein expressed by the peripheral nervous system Schwann cells is protein zero (P0), which represents 50% of the total protein content in myelin. This 30-kDa integral membrane protein consists of an immunoglobulin (Ig)-like domain, a transmembrane helix, and a 69-residue C-terminal cytoplasmic tail (P0ct). The basic residues in P0ct contribute to the tight packing of myelin lipid bilayers, and alterations in the tail affect how P0 functions as an adhesion molecule necessary for the stability of compact myelin. Several neurodegenerative neuropathies are related to P0, including the more common Charcot-Marie-Tooth disease (CMT) and Dejerine-Sottas syndrome (DSS) as well as rare cases of motor and sensory polyneuropathy. We found that high P0ct concentrations affected the membrane properties of bicelles and induced a lamellar-to-inverted hexagonal phase transition, which caused bicelles to fuse into long, protein-containing filament-like structures. These structures likely reflect the formation of semicrystalline lipid domains with potential relevance for myelination. Not only is P0ct important for stacking lipid membranes, but time-lapse fluorescence microscopy also shows that it might affect membrane properties during myelination. We further describe recombinant production and low-resolution structural characterization of full-length human P0. Our findings shed light on P0ct effects on membrane properties, and with the successful purification of full-length P0, we have new tools to study the role of P0 in myelin formation and maintenance in vitro.

Edukasi Penerapan Terapi Bermain Puzzle Sederhana Untuk Perkembangan Motorik Halus Pada Anak Usia 3-6 Tahun Di UPT Puskesmas Kedaton Bandar Lampung

Fine motor skills are movements carried out by the fingers with a central nervous cell arrangement that regulates the use of small muscle groups such as the fingers and hands, and often require precision and coordination with the hands. One type of game that can optimize children's fine motor development is puzzle games. Puzzles are a type of game that improves thinking skills, makes it easier to remember and understand concepts, and increases creativity. Puzzle games are simple games that are played in pairs and require precision because children are trained to focus their minds so they can concentrate. The aim of this activity is to improve fine motor development in children through puzzle play therapy. It was found that respondents were very enthusiastic about carrying out play therapy. The conclusion from this activity is that fine motor development in children can be trained using puzzle play therapy.

GCT-15. CLINICAL AND MOLECULAR CHARACTERIZATION OF INFANTILE CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Abstract BACKGROUND The management of infantile central nervous system germ cell tumors (CNS-GCTs) presents unique challenges, including variable clinical presentations such as tumor size and propensity for hemorrhage. Moreover, data on the clinical and molecular features remain limited. METHODS We conducted a clinical and molecular analysis of CNS-GCTs in children aged 6 years or younger, registered with the Japan Children’s Cancer Group and the iGCT consortium. DNA methylation analysis was performed using the Illumina Methylation EPIC array to identify potential molecular prognostic indicators. RESULTS The cohort comprised 43 patients, with a median age at onset of 6.5 months (0–68 months). Notably, 23 patients (54%) were diagnosed before 1 year of age. The male-female ratio was 27:15. Most common tumor location was cerebellum (13 cases). The median AFP level was 538 ng/ml (0–206460). Pathologically, the tumors were predominantly diagnosed as teratomas and yolk sac tumors. Teratomas were more common in patients diagnosed before 1 year of age, while mixed GCTs were more frequent in those diagnosed after 3 years. Molecular analysis identified four cases as embryonal tumors, including three AT/RTs and one DICER1-mutant intracranial sarcoma. The 3-year overall survival rates varied significantly by diagnosis: mixed GCTs at 100%, teratomas at 90.6%, yolk sac tumors at 30.0%, and embryonal tumors at 0%. Notably, two patients with teratomas developed metachronous tumors more than 10 years post-diagnosis, with both secondary tumors exhibiting mutations in the MAPK pathway absent in the primary tumors. CONCLUSION Infantile CNS-GCTs exhibit distinct clinical and molecular profiles compared to those in older children and adults. Not all tumors classified as GCTs based on molecular characterization were GCTs; some were embryonal tumors, potentially impacting treatment strategy. The genetic analysis suggests that some metachronous GCTs may represent second primary tumors rather than recurrences.

From the Microbiome to the Electrome: Implications for the Microbiota-Gut-Brain Axis.

The gut microbiome plays a fundamental role in metabolism, as well as the immune and nervous systems. Microbial imbalance (dysbiosis) can contribute to subsequent physical and mental pathologies. As such, interest has been growing in the microbiota-gut-brain brain axis and the bioelectrical communication that could exist between bacterial and nervous cells. The aim of this study was to investigate the bioelectrical profile (electrome) of two bacterial species characteristic of the gut microbiome: a Proteobacteria Gram-negative bacillus Escherichia coli (E. coli), and a Firmicutes Gram-positive coccus Enterococcus faecalis (E. faecalis). We analyzed both bacterial strains to (i) validate the fluorescent probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, DiBAC4(3), as a reliable reporter of the changes in membrane potential (Vmem) for both bacteria; (ii) assess the evolution of the bioelectric profile throughout the growth of both strains; (iii) investigate the effects of two neural-type stimuli on Vmem changes: the excitatory neurotransmitter glutamate (Glu) and the inhibitory neurotransmitter γ-aminobutyric acid (GABA); (iv) examine the impact of the bioelectrical changes induced by neurotransmitters on bacterial growth, viability, and cultivability using absorbance, live/dead fluorescent probes, and viable counts, respectively. Our findings reveal distinct bioelectrical profiles characteristic of each bacterial species and growth phase. Importantly, neural-type stimuli induce Vmem changes without affecting bacterial growth, viability, or cultivability, suggesting a specific bioelectrical response in bacterial cells to neurotransmitter cues. These results contribute to understanding the bacterial response to external stimuli, with potential implications for modulating bacterial bioelectricity as a novel therapeutic target.

The Mechanisms of Mesenchymal Stem Cells in the Treatment of Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and is a leading cause of disability in young adults. Most therapeutic strategies are based on immunosuppressant effects. However, none of the drugs showed complete remission and may result in serious adverse events such as infection. Mesenchymal stem cells (MSCs) have gained much attention and are considered a potential therapeutic strategy owing to their immunomodulatory effects and neuroprotective functions. Experimental autoimmune encephalomyelitis (EAE), a classical animal model for MS, is widely used to explore the efficacy and mechanism of MSC transplantation. This review summarises the therapeutic mechanism of MSCs in the treatment of EAE, including the effects on immune cells (T cells, B cells, dendritic cells, natural killer cells) and central nervous system-resident cells (astroglia, microglia, oligodendrocytes, neurons) as well as various strategies to improve the efficacy of MSCs in the treatment of EAE. Additionally, we discuss the clinical application of MSCs for MS patients as well as the challenges and prospects of MSC transplantation.

Evaluation of intravenous magnesium sulphate on haemodynamic responses to laryngoscopy and tracheal intubation in surgeries of ear, nose and throat

Heart rate, arterial blood pressure, and arrhythmias significantly surge during laryngoscopy and intubation. Anesthesiologists constantly look for ways to minimize these unwanted reactions. Several medicinal interventions have been suggested to mitigate these side effects; intravenous magnesium sulphate injection is one such intervention. Magnesium sulphate is a divalent salt widely recognized for its capacity to lower sympathetic nervous system muscle cell excitability, which lowers blood pressure and causes vasodilation. It is approved as a medicine to treat preeclampsia and control blood pressure. Moreover, there is growing recognition of its benefits on hemodynamic parameters in patients suffering from ischemic infective endocarditis and heart disease. Magnesium is an asset for reducing negative cardiovascular reactions occurring at the time of laryngoscopy and intubation because of its capacity to reduce catecholamine synthesis from adrenergic nerve ends and the adrenal medulla. Intravenous magnesium sulphate will be used in this trial to assess its effect on reducing adverse hemodynamic responses in candidates for elective laryngoscopy and intubation for ENT surgeries.

Dopamine and its precursor levodopa inactivate SARS-CoV-2 main protease by forming a quinoprotein

Many studies show either the absence, or very low levels of, SARS-CoV-2 viral RNA and/or antigen in the brain of COVID-19 patients. Reports consistently indicate an abortive infection phenomenon in nervous cells despite the fact that they contain the SARS-CoV-2 receptor, ACE2. Dopamine levels in different brain regions are in the range of micromolar to millimolar concentrations. We have shown that sub-micromolar to low micromolar concentrations of dopamine or its precursor (levodopa) time- and dose-dependently inhibit the activity of SARS-CoV-2 main protease (Mpro), which is vital for the viral life cycle, by forming a quinoprotein. Thiol detection coupled with the assessment of Mpro activity suggests that among the 12 cysteinyl thiols, the active site, Cys145-SH, is preferentially conjugated to the quinone derived from the oxidation of dopamine or levodopa. LC-MS/MS analyses show that the Cys145-SH is covalently conjugated by dopamine- or levodopa-o-quinone. These findings help explain why SARS-CoV-2 causes inefficient replication in many nerve cell lines. It is well recognized that inhaled pulmonary drug delivery is the most robust therapy pathway for lung diseases. CVT-301 (orally inhaled levodopa) was approved by the FDA as a drug for Parkinson's patients prior to the outbreak of COVID-19 in 2018. Based on the fact that SARS-CoV-2 causes inefficient replication in the CNS with abundant endogenous Mpro inhibitor in addition to the current finding that levodopa has an Mpro-inhibitory effect somewhat stronger than dopamine, we should urgently investigate the use of CVT-301 as a lung-targeting, COVID-19, Mpro inhibitor.

CNS Germ Cell Tumors: Molecular Advances, Significance in Risk Stratification and Future Directions.

Central Nervous System Germ Cell Tumors (CNS GCTs) represent a subtype of intracranial malignant tumors characterized by highly heterogeneous histology. Current diagnostic methods in clinical practice have notable limitations, and treatment strategies struggle to achieve personalized therapy based on patient risk stratification. Advances in molecular genetics, biology, epigenetics, and understanding of the tumor microenvironment suggest the diagnostic potential of associated molecular alterations, aiding risk subgroup identification at diagnosis. Furthermore, they suggest the existence of novel therapeutic approaches targeting chromosomal alterations, mutated genes and altered signaling pathways, methylation changes, microRNAs, and immune checkpoints. Moving forward, further research is imperative to explore the pathogenesis of CNS GCTs and unravel the intricate interactions among various molecular alterations. Additionally, these findings require validation in clinical cohorts to assess their role in the diagnosis, risk stratification, and treatment of patients.

Melatonin suppresses TLR4-mediated RSV infection in the central nervous cells by inhibiting NLRP3 inflammasome formation and autophagy.

Respiratory syncytial virus (RSV) infects neuronal cells in the central nervous system (CNS), resulting in neurological symptoms. In the present study, we intended to explore the mechanism of RSV infection-induced neuroinflammatory injury from the perspective of the immune response and sought to identify effective protective measures against the injury. The findings showed that toll-like receptor 4 (TLR4) was activated after RSV infection in human neuronal SY5Y cells. Furthermore, TLR4 activation induced autophagy and apoptosis in neuronal cells, promoted the formation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and increased the secretion of downstream inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumour necrosis factor-α (TNF-α). Interestingly, blockade of TLR4 or treatment with exogenous melatonin significantly suppressed TLR4 activation as well as TLR4-mediated apoptosis, autophagy and immune responses. Therefore, we infer that melatonin may act on the TLR4 to ameliorate RSV-induced neuronal injury, which provides a new therapeutic target for RSV infection.

The molecular determinants of microglial developmental dynamics.

Microglia constitute the largest population of parenchymal macrophages in the brain and are considered a unique subset of central nervous system glial cells owing to their extra-embryonic origins in the yolk sac. During development, microglial progenitors readily proliferate and eventually colonize the entire brain. In this Review, we highlight the origins of microglial progenitors and their entry routes into the brain and discuss the various molecular and non-molecular determinants of their fate, which may inform their specific functions. Specifically, we explore recently identified mechanisms that regulate microglial colonization of the brain, including the availability of space, and describe how the expansion of highly proliferative microglial progenitors facilitates the occupation of the microglial niche. Finally, we shed light on the factors involved in establishing microglial identity in the brain.

Molecular Biomarkers of Neurodegenerative Disorders: A Practical Guide to Their Appropriate Use and Interpretation in Clinical Practice.

Neurodegenerative disorders (NDs) represent a group of different diseases characterized by the progressive degeneration and death of the nervous system's cells. The diagnosis is challenging, especially in the early stages, due to no specific clinical signs and symptoms. In this context, laboratory medicine could support clinicians in detecting and differentiating NDs. Indeed, biomarkers could indicate the pathological mechanisms underpinning NDs. The ideal biofluid for detecting the biomarkers of NDs is cerebrospinal fluid (CSF), which has limitations, hampering its widespread use in clinical practice. However, intensive efforts are underway to introduce high-sensitivity analytical methods to detect ND biomarkers in alternative nonivasive biofluid, such as blood or saliva. This study presents an overview of the ND molecular biomarkers currently used in clinical practice. For some diseases, such as Alzheimer's disease or multiple sclerosis, biomarkers are well established and recommended by guidelines. However, for most NDs, intensive research is ongoing to identify reliable and specific biomarkers, and no consensus has yet been achieved.