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

Sunil S. Adav and Siu Kwan Sze

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64693

#### **Abstract**

[106] Koronyo Y, Salumbides, BC, Black KL, Koronyo-Hamaoui M. Alzheimer's disease in the retina: imaging retinal aβ plaques for early diagnosis and therapy assessment.

[107] Park YD, Park JH, Hur MG, Kim SW, Min JJ, Park SH, et al. Fluorescent 2-styrylpyri‐ dazin-3(2H)-one derivatives as probes targeting amyloid-beta plaques in Alzheimer's

disease. Bioorganic & Medicinal Chemistry Letters. 2012;22(12):4106–10.

Neurodegeneration Diseases. 2012;10(1–4):285–93.

108 Update on 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, accumu‐ lates 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 aggrega‐ tion mechanism that may lead to dementia. We attempted to correlate DPMs and its impact on protein aggregation and deposition in brain tissues.

**Keywords:** dementia, Alzheimer's disease, vascular dementia, neurodegenerative dis‐ ease, proteomics, degenerative protein modifications (DPMs), deamidation, citrullina‐ tion, amyloid

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
