Fig. 6.

Schematic hypothesis of cellular regulation of SNCA transcripts during the maturation process of Lewy body formation A In healthy condition, neurons express physiological levels of SNCA transcripts, and their protein degradation systems function normally. B When a “neurodegenerative event” occurs, (e.g. protein degradation system dysfunction) monomeric α-synuclein (α-syn) misfolds and serves as seeds for further disease propagation. Additionally, α-syn seeds are internalized from the extracellular space. Punctate α-syn immunoreactivity is observed in the cytoplasm in both cases. The neuron tries to ‘sequester’ misfolded α-syn. Due to the misfolding of α-syn, its physiological function is impaired. The neuron attempts to preserve physiological functioning by maintaining normal levels of SNCA transcripts. C Neurons reach a critical state and either (1) the misfolded α-syn is segregated into Lewy body, SNCA transcripts reduce due to cell dysfunction, ultimately leading to neuronal death, or, (2) the misfolded α-syn directly leads to neuronal death. Expression level of monomeric α-syn is preserved during the progression of the disease. Created with BioRender.com