Proteomic Study of Degenerative Protein Modifications in the Molecular Pathology of Neurodegeneration and Dementia

Dementia is a major public health burden, and the World Health Organization has identified this disorder as a major public health priority. There are limited treatment options due to poor understanding of key mechanism of dementia pathogenesis. Dementia has been regarded as a proteinopathy in which alterations of brain protein structure and function are the key features of the disorder. Proteinopathy can be triggered by degenerative protein modifications (DPMs), misfolding, aggregation, and deposition of the malformed proteins. Despite the clinical significance of alteration in protein abundances, DPMs, protein misfolding, and aggregation, the molecular mechanism that promotes these changes remains inadequately understood, mostly due to technical challenges. Proteomic is a powerful, sensitive, and advanced tool to study the progressive brain tissue damage that critically dysregulates key enzymes, accumulates modified proteins, and causes protein misfolding and aggregation, resulting in cognitive decline and dementia. The proteomic profiling of protein abundances and correlating DPMs with protein misfolding and aggregation have potential to elucidate underlying molecular mechanism of the disease. This chapter summarizes the recent proteomic developments for studying brain proteome, DPMs, and protein aggregation mechanism that may lead to dementia. We attempted to correlate DPMs and its impact on protein aggregation and deposition in brain tissues.