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.
