Role of Amyloidogenic and Non-Amyloidogenic Protein Spaces in Neurodegenerative Diseases and Their Mitigation Using Theranostic Agents.

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 NDDs except a few such as donepezil, rivastigmine, galantamine, carbidopa and levodopa which treat the disease-associated-symptoms. Similarly, there are few FDA-approved tracers such as flortaucipir for tau fibril-imaging and florbetaben, flutemetamol, and florbetapir for amyloid-imaging available for diagnosis. Recent advances in the cryo-EM 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 discuss various proteins associated with NDDs and their implications in NDD. In addition, we document  chemical compounds developed for diagnosis and therapy of different NDDs with special emphasis on theranostic agents.