BDNF in PD - Nature
Miller, Mercado, Sortwell/Nature/2021
Why It Matters
This paper caught my attention because it connects the protein clumps that define Parkinson's (Lewy bodies) to a measurable deficit in BDNF—a growth factor that keeps neurons healthy. If the relationship holds up, it suggests that strategies to boost BDNF (exercise, certain supplements, or future drugs) might slow neurodegeneration in PD. Important caveat: this is based heavily on cell culture models using preformed alpha-synuclein fibrils, not human clinical data, so we're still early in understanding what this means for actual patients.
Key Findings
- Lewy bodies in human Parkinson's brain tissue correlate with altered expression of hundreds of neuronal proteins and genes, indicating widespread cellular dysfunction beyond simple protein aggregation
- Lab models using alpha-synuclein preformed fibrils (PFFs) to mimic Lewy body formation show a pronounced and relatively unique reduction in BDNF expression—more so than other neurotrophic factors
- BDNF has known protective effects on dopamine neurons in the basal ganglia, including promoting survival, supporting synaptic function, and potentially enhancing neuroplasticity
- The alpha-synuclein PFF model replicates key features of human Lewy pathology in cell culture, making it useful for studying what goes wrong inside neurons when these clumps form
- What remains untested is whether increasing BDNF can actually reverse or prevent the cellular damage caused by alpha-synuclein inclusions in living systems