Abstract
Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson’s disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the disease; therefore, new therapeutical approaches are needed. Since, in both PD patients and animal PD models, decreased level of BDNF was found in the nigrostriatal pathway, it has been hypothesized that BDNF may serve as a therapeutic agent. Direct delivery of exogenous BDNF into the patient’s brain did not relieve the symptoms of disease, nor did attempts to enhance BDNF expression with gene therapy. Physical training was neuroprotective in animal models of PD. This effect is mediated, at least partly, by BDNF. Animal studies revealed that physical activity increases BDNF and tropomyosin receptor kinase B (TrkB) expression, leading to inhibition of neurodegeneration through induction of transcription factors and expression of genes related to neuronal proliferation, survival, and inflammatory response. This review focuses on the evidence that increasing BDNF level due to gene modulation or physical exercise has a neuroprotective effect and could be considered as adjunctive therapy in PD.
Highlights
Brain-derived neurotrophic factor (BDNF) belongs to neurotrophins (NTs)—a family of proteins that support the function of the central nervous system (CNS)
BDNF plays a key role in the development of the nervous system by affecting cell differentiation, neuronal development, growth and survival, neurogenesis, synaptogenesis, and synaptic plasticity [7,8,9,10]
ProBDNF and mature BDNF (mBDNF) exert their biological activity by binding to two types of cell surface receptors, the Trk tyrosine kinases and the p75 neurotrophin receptor (p75NTR) [34]. They often have an opposite effect on survival, differentiation, growth, and apoptosis of neurons; the proBDNF/mBDNF balance is an important factor inf the regulation of many processes in CNS [35,36]. mBDNF binds with a high affinity to the tropomyosin receptor kinase B (TrkB) receptor, while proBDNF has a greater affinity to the p75NTR, through its mature domain and to the sortilin receptor through the prodomain
Summary
Brain-derived neurotrophic factor (BDNF) belongs to neurotrophins (NTs)—a family of proteins that support the function of the central nervous system (CNS). It was shown that neurodegenerative and neuropsychiatric diseases may be partially caused by defects in synaptic plasticity associated with the insufficient neuronal supply of BDNF and other neurotrophic factors [11,12,13]. ProBDNF and mBDNF exert their biological activity by binding to two types of cell surface receptors, the Trk tyrosine kinases and the p75 neurotrophin receptor (p75NTR) [34]. They often have an opposite effect on survival, differentiation, growth, and apoptosis of neurons; the proBDNF/mBDNF balance is an important factor inf the regulation of many processes in CNS [35,36]. 6-8-week-old Bdnf +/− mice showed worse performance in Morris Water Maze than control animals, whereas 10-month-old Bdnf +/− animals did not learn at all, suggesting that the BDNF may alter learning abilities [83]
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