Protein Metabolism: Critical Factors Implicated in Neurodegenerative Diseases

Protein metabolism involves protein synthesis, posttranslational modifications, and protein folding. Cell has protein quality control systems like ubiquitin-proteasome system and autophagy to degrade misfolded protein. All these processes are precisely regulated to maintain proper proteostasis and homeostasis. Alteration in these processes such as anomalous posttranslational modifications, misfolding, and aberrant protein quality control system results in accumulation and mis-localization of proteins. The aggregated proteins consequently leads to protein toxicity and neuronal death. Formation of aggresome and disrupted proteostasis is the hallmark of neurodegeneration. This chapter highlights the pivotal role of protein homeostasis in neurodegeneration. The crucial role of amyloid-β, α-synuclein, and tau proteins and their processing defects results in aggregate formation in a variety of neurodegenerative diseases and these have been discussed in detail. Additionally, the molecular mechanisms associated with aggregation like posttranslational modifications, such as acetylation, phosphorylation, and ubiquitination have been also described. Defects in the components of ubiquitin machinery and autophagy results in epigenetic and transcriptional dysfunction, abnormal nucleocytoplasmic transport, mitochondrial defects, and increased ROS production along with altered stress granule dynamics and morphology.