Background

Neurodegenerative diseases (ND) can be classified according to primary clinical features (e.g., dementia, parkinsonism, or motor neuron disease), anatomic distribution of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), or principal molecular abnormality.
The most common neurodegenerative disorders are amyloidoses, tauopathies, a-synucleinopathies, and TDP-43 proteinopathies.
Characteristics of ND:
- protein abnormalities that define ND can be present before the onset of clinical features.
- More than one ND process can be found in an individual.
- ND share many fundamental processes associated with progressive neuronal dysfunction and death, such as proteotoxic stress and its attendant abnormalities in ubiquitin-proteasomal and autophagosomal/lysosomal systems, oxidative stress, programmed cell deat and neuroinflammation.

Classification

The most common neurodegenerative dis- orders are amyloidoses, tauopathies, a-synucleinopathies, and transactivation response DNA binding protein 43 (TDP-43) proteinopathies.

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Lewy body disorders include parkinson disease (PD), PD with dementia, and dementia with lewy bodies.

Disease	Specifics of Protein
Amyloidoses	Amyloids are insoluble fibrous proteins that have specific structural characteristics, including a beta-sheet-rich secondary structure, which permits binding by specific dyes, such as Congo red.
The most common amyloidosis is a proteolytic product of the amyloid precursor protein, which is encoded by a gene on chromosome 21 (Kang et al. 1987), and is referred to as beta- amyloid or A-beta
Taupathies	Tau is a microtubule-associated phosphoprotein abundant in axons involved in promoting polymerization and stabilization of microtubules.
In addition to phosphorylation, tau undergoes other post-translational modifications, such as ubiquitination, nitration, glycation, and acetylation, all of which have been linked to abnormal tau that accumulates in degenerative tauopathies
Synucleinopathies	This class of neurodegenerative diseases is characterized by aggregation of the presynaptic protein, a-synuclein, within neurons and glia (mostly oligodendroglia). It is a 140- amino-acid protein initially discovered as a non-amyloid component of senile plaques (NACP) in AD.
TDP-43 Proteinopathies	TDP-43 is a 43-kDa protein that can function in transcriptional repression, modulating gene splicing, RNA metabolism, and stress granules. TDP-43 is normally a nuclear protein, but in neurodegenerative diseases, it forms inclusion bodies in the cytoplasm, nucleus, and cell processes.

References

Dugger BN, Dickson DW. Pathology of Neurodegenerative Diseases. Cold Spring Harbor Perspectives in Biology. 2017 Jul [cited 2023 September 14]; 9(7):a028035. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495060/. doi: 10.1101/cshperspect.a028035

Pathology of Neurodegenerative Diseases 2017.pdf