The role of altered protein acetylation in neurodegenerative disease

Published on January 4, 2023

Just like adding toppings to a pizza can change its flavor and texture, acetylation modifies proteins to regulate important cellular processes. It’s like a key that controls DNA transcription, aging, and even memory and learning in our brain cells. But when this process goes haywire, it can have devastating consequences for neurological health. Imagine if the pizza toppings were completely mixed up and didn’t taste right – that’s what happens when proteins become hyperacetylated or hypoacetylated in neurodegenerative diseases like Alzheimer’s, Parkinson’s, Huntington’s, and ALS. These disorders are like a symphony being thrown off balance, with the accumulation of pathophysiological proteins disrupting the normal functioning of the brain. The good news is that scientists are actively studying altered protein acetylation in these diseases to unravel their underlying mechanisms and potentially develop targeted treatments. If you’re curious about how this intricate process goes wrong, check out the research article below!

Acetylation is a key post-translational modification (PTM) involved in the regulation of both histone and non-histone proteins. It controls cellular processes such as DNA transcription, RNA modifications, proteostasis, aging, autophagy, regulation of cytoskeletal structures, and metabolism. Acetylation is essential to maintain neuronal plasticity and therefore essential for memory and learning. Homeostasis of acetylation is maintained through the activities of histone acetyltransferases (HAT) and histone deacetylase (HDAC) enzymes, with alterations to these tightly regulated processes reported in several neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). Both hyperacetylation and hypoacetylation can impair neuronal physiological homeostasis and increase the accumulation of pathophysiological proteins such as tau, α-synuclein, and Huntingtin protein implicated in AD, PD, and HD, respectively. Additionally, dysregulation of acetylation is linked to impaired axonal transport, a key pathological mechanism in ALS. This review article will discuss the physiological roles of protein acetylation and examine the current literature that describes altered protein acetylation in neurodegenerative disorders.

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