Neurotrophic Factors in Parkinson's Disease Pathophysiology
Summary
Neurotrophic factors are a class of signalling proteins vital for the survival, growth and maintenance of neurons. In Parkinson’s disease, the progressive loss of dopaminergic neurons within the substantia nigra leads to the cardinal motor symptoms, and mounting evidence implicates dysregulated neurotrophic support in this degeneration. Reduced levels of key factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factors (IGFs) and transforming growth factor-β have been reported in both patient tissues and experimental models, correlating with mitochondrial dysfunction, oxidative stress and impaired synaptic plasticity. Restoration of neurotrophic signalling has therefore emerged as a promising therapeutic strategy. Experimental approaches range from gene therapy to small-molecule agonists targeting specific receptors, aiming to bolster endogenous repair pathways and attenuate α-synuclein aggregation. Understanding the interplay between distinct trophic pathways offers new avenues to slow or even reverse the neurodegenerative cascade.
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Neurotrophic Factors in Parkinson's Disease Pathophysiology publication trend
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Technical terms
Neurotrophic factor: A protein that supports neuron survival, differentiation and synaptic plasticity.
Dopaminergic neuron: A nerve cell that produces and releases dopamine, critical for motor control.
α-Synuclein: A presynaptic protein whose misfolding and aggregation are hallmarks of Parkinson’s disease.
Brain-derived neurotrophic factor (BDNF): A neurotrophin that promotes survival and growth of neurons via TrkB receptors.
Insulin-like growth factor 2 (IGF2): A growth factor involved in neuronal survival and protein clearance mechanisms.
Tropomyosin receptor kinase B (TrkB): The high-affinity receptor for BDNF, triggering intracellular cascades that support neuron function.
References
- IGF2 prevents dopaminergic neuronal loss and decreases intracellular alpha-synuclein accumulation in Parkinson’s disease models. Cell Death Discovery (2023).
- Insulin‐Like Growth Factor Binding Protein 2 Drives Neurodegeneration in Parkinson's Disease: Insights From In Vivo and In Vitro Studies. CNS Neuroscience & Therapeutics (2024).
- BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy. Journal of Cellular and Molecular Medicine (2024).
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