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. Thefocal 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.