Nanomedicine and Neurodegenerative Diseases: An Introduction to Pathology and Drug Targets

Neurodegenerative diseases are debilitating conditions that result in progressive degeneration and death of neuronal cells. One of the hallmarks of neurodegenerative diseases is the formation of protein aggregates. Progressive accumulation of similar protein aggregates is recognized as a characteristic feature of many neurodegenerative diseases. Particularly in Parkinson’s Disease (PD), aggregated forms of the protein α-synuclein (α-syn); and in Alzheimer's Disease (AD) and cerebral amyloid angiopathy (CAA), aggregated Aβ amyloid fibrils form the basis of parenchymal plaques and of perivascular amyloid deposits, respectively. In Amyotrophic Lateral Sclerosis (ALS), the RNA-binding protein TDP-43 is prone to aggregation. The focal aggregates at early disease stages later on result in the spreading of deposits into other brain areas and many neurodegenerative diseases display a characteristic spreading pattern. Here, we will summarize the anatomy and pathology of the predominant neurodegenerative diseases focusing on AD and PD and review their clinical manifestation to highlight the urge of novel therapeutic strategies. Additionally, given that development of treatments requires suitable animal models, the most commonly used model systems are introduced and their pathology compared to the human situation is mentioned briefly. Finally, possible drug targets in neurodegenerative diseases are discussed.

Keywords: Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, Animal models, Drug targets, Dementia, Lewy Bodies, Neurodegeneration, Parkinson’s Disease, Synuclein, TDP-43 Tau pathology, β-Amyloid.