Biochemical and Molecular Pathways in Neurodegenerative Diseases: An Integrated View

Cells. 2023 Sep 20;12(18):2318. doi: 10.3390/cells12182318.

Abstract

Neurodegenerative diseases (NDDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are defined by a myriad of complex aetiologies. Understanding the common biochemical molecular pathologies among NDDs gives an opportunity to decipher the overlapping and numerous cross-talk mechanisms of neurodegeneration. Numerous interrelated pathways lead to the progression of neurodegeneration. We present evidence from the past pieces of literature for the most usual global convergent hallmarks like ageing, oxidative stress, excitotoxicity-induced calcium butterfly effect, defective proteostasis including chaperones, autophagy, mitophagy, and proteosome networks, and neuroinflammation. Herein, we applied a holistic approach to identify and represent the shared mechanism across NDDs. Further, we believe that this approach could be helpful in identifying key modulators across NDDs, with a particular focus on AD, PD, and ALS. Moreover, these concepts could be applied to the development and diagnosis of novel strategies for diverse NDDs.

Keywords: Alzheimer’s disease; Parkinson’s disease; ageing; amyotrophic lateral sclerosis; autophagy; calcium butterfly effect; chaperones; excitotoxicity; mitophagy; neurodegenerative diseases; neuroinflammation; oxidative stress; proteostasis.

Publication types

  • Review

Grants and funding

This research was funded by the Research Manitoba 2017 Health Research New Investigator Operating Grant, Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant, and Canadian Institutes of Health Research (CIHR) Bridge grant to G.K.T.