Role of Amyloidogenic and Non‐Amyloidogenic Protein Spaces in Neurodegenerative Diseases and their Mitigation Using Theranostic Agents

• Published in: Chembiochem : a European journal of chemical biology Vol. 25; no. 13; pp. e202400224 - n/a
• Main Authors: Suri, Kapali, Ramesh, Madhu, Bhandari, Mansi, Gupta, Vishakha, Kumar, Virendra, Govindaraju, Thimmaiah, Murugan, N. Arul
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 02.07.2024
• Subjects: Alzheimer's disease; Amyloid and non-amyloid Protein Space; Amyloidogenesis; Chemical compounds; Chemical spaces; Dementia disorders; Diagnosis; Disease; Donepezil; Drug development; Electron microscopy; Fibrils; Galantamine; Levodopa; Medical imaging; Neurodegenerative diseases; Neuroimaging; Proteins; Reagents; Rivastigmine; Signs and symptoms; Tau protein; Theranostic agents; Amyloid and Non-amyloid Protein Space; Chemical space; Theranostic agents; Neurodegenerative diseases; Alzheimer's disease
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.202400224

Neurodegenerative diseases (NDDs) refer to a complex heterogeneous group of diseases which are associated with the accumulation of amyloid fibrils or plaques in the brain leading to progressive loss of neuronal functions. Alzheimer's disease is one of the major NDD responsible for 60–80 % of all dementia cases. Currently, there are no curative or disease‐reversing/modifying molecules for many of the NDDs except a few such as donepezil, rivastigmine, galantamine, carbidopa and levodopa which treat the disease‐associated symptoms. Similarly, there are very few FDA‐approved tracers such as flortaucipir (Tauvid) for tau fibril imaging and florbetaben (Neuraceq), flutemetamol (Vizamyl), and florbetapir (Amyvid) for amyloid imaging available for diagnosis. Recent advances in the cryogenic electron microscopy reported distinctly different microstructures for tau fibrils associated with different tauopathies highlighting the possibility to develop tauopathy‐specific imaging agents and therapeutics. In addition, it is important to identify the proteins that are associated with disease development and progression to know about their 3D structure to develop various diagnostics, therapeutics and theranostic agents. The current article discusses in detail the disease‐associated amyloid and non‐amyloid proteins along with their structural insights. We comprehensively discussed various novel proteins associated with NDDs and their implications in disease pathology. In addition, we document various emerging chemical compounds developed for diagnosis and therapy of different NDDs with special emphasis on theranostic agents for better management of NDDs. Neurodegenerative diseases (NDDs) encompass a spectrum of overlapping disorders marked by abnormal protein aggregation, resulting in the formation of toxic amyloid aggregation species. Additionally, these diseases involve dysregulated expression and function of proteins associated with various overlapping pathologies. This review delves into the protein fibril spaces linked to NDDs. Furthermore, evolving theranostic agents, which serve as valuable chemical tools, aid in both diagnosis and treatment, contributing to the improved management of these intricate disorders are discussed.