A Bioinformatic Analysis of BAG Protein Interactors and Pathways in Alzheimer’s and Parkinson’s Disease

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Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative disorders. While the symptoms and general etiology may be different, these two diseases share significant common features in terms of their disease pathogenesis. Within the scope of neurodegenerative disorders, the Bcl-2 associated athanogene (BAG) family proteins and associated interactors have been a key area of focus. The BAG family is a group of proteins that contain at least one evolutionarily conserved BAG domain. Despite this similarity, their interactions and functions can vary widely. So far, research has predominantly scrutinized individual BAG proteins, rather than explore potential cooperative actions among family members. Some BAG family members may function together thereby indicating potential interactions within this family. Although connections among BAG members have been observed, their role in neurodegenerative disorders, such as AD and PD, remains largely uncharacterized. This mini review explores the common pathways, intersections, and differences within these interactions as well as their link to AD and PD. Using computational techniques to mine transcriptomic data, several groupings of pathways that these BAG family members are involved in were identified in the context of AD and PD. Understanding these pathways and their relationships may uncover potential gaps in current research and help identify novel therapeutic targets for the treatment of these neurodegenerative diseases.

Significance statement

Although distinct diseases, Alzheimer’s disease and Parkinson’s disease share common features such as protein aggregation and mitochondrial dysfunction. Members of the BAG family of proteins have been implicated in the pathogenesis of both diseases. Computational techniques were used to mine transcriptomic data of Alzheimer’s and Parkinson’s disease cases to identify common pathways. BAG protein interactors, common to all family members, were analyzed in the context of these common pathways for Alzheimer’s and Parkinson’s disease. These analyses provide insights into the pathways mediated by these BAG protein interactors that are likely at the intersection of Alzheimer’s disease and Parkinson’s disease pathologies.

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