An introduction to neurodegenerative disorders: Pathophysiology, hallmarks, and mechanisms at a glance

Neurodegenerative diseases involve the gradual decline of specific vulnerable neuronal populations, as opposed to static neuronal loss seen in metabolic or toxic diseases. These conditions can be categorized based on clinical features (e.g., dementia, Parkinson's disease), anatomical distribution (e.g., anterior temporal lobe degeneration), or significant molecular abnormalities. Common adult neurodegenerative diseases are polyglutamine disorders, Alzheimer’s, frontotemporal lobe degeneration, Parkinson’s, multiple system atrophies, etc. Most neurodegenerative diseases exhibit protein aggregation, like amyloid-β and tau in Alzheimer's disease, α-synuclein in Parkinson's disease, and TAR DNA-binding protein 43 in amyotrophic lateral sclerosis. Several models and studies provide escalating proof regarding intercellular transmission and amplification of such misfolded protein aggregates playing a role in the initiation and advancement of several neurodegenerative disorders. These transferred misfolded proteins are commonly known as “pathological seeds.” Neurodegenerative diseases often share common pathophysiological elements, with oxidative stress (OS) and inflammatory responses being the key contributors. Unfortunately, these conditions pose challenges for effective treatment. Given the burden imposed by the progression of these diseases and the lack of efficient treatments, there is widespread exploration of therapeutic approaches aimed at intercepting the development of neurodegeneration. This chapter focuses on common neurodegenerative diseases, aiming to contribute to a more comprehensive future study of these conditions.