Does altering proteasomal activity and trafficking reduce the arborization mediated specific vulnerability of SNpc dopaminergic neurons of Parkinson's disease?

Smitha Bhaskar, Jeevan Gowda, Jyothi Prasanna, Anujith Kumar

Research output: Contribution to journalArticle

Abstract

Parkinson's disease (PD) is a late-onset degenerative neuronal disorder and stands second among the neurological disorders with 1% of the total world population being affected. The disease originates majorly due to compromised function of the dopaminergic (DA) neurons in the Substantia Nigra pars compacta (SNpc), but not the ventral tegmental area (VTA) region of the midbrain. The differential susceptibility for degeneration is majorly attributed to morphological, molecular, and electrophysiological heterogeneity existing in DA neurons of SNpc and VTA. Long-range axonal arborization and a higher number of synapses in SNpc DA neurons make it more vulnerable compared to VTA DA neurons. Studies have shown that a decrease in such axonal arborization places DA neurons at decreased risk in PD. The two well established underlying mechanisms are a) As arborization is an energy-demanding process, increased redistribution of mitochondria to the axonal terminals occurs to satisfy the bioenergetic requirement b) The stabilization of axon-promoting factors at the axonal tip is an essential component for enhancing the arborization process. Interfering with any of these two processes would probably alleviate the degeneration of SNpc DA neurons. To accomplish the decreased stability of arborizing factors and thereby increase the resilience of SNpc DA neurons, we hypothesize the activation of anterograde transport-dependent recruitment of proteasomes to axon terminals as one of the most favorable approaches. Understanding this putative avenue of enhancing proteasomal activity and migration to the axonal tip could provide insight into the progression of neurodegeneration in PD and possibly offer a novel therapeutic strategy.

Original languageEnglish
Article number110062
JournalMedical Hypotheses
Volume143
DOIs
Publication statusPublished - 10-2020

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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