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Abnormal phosphorylation of protein tyrosine in neurodegenerative diseases

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OXFORD UNIV PRESS INC
DOI: 10.1093/jnen/nlad066

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Alzheimer disease; Multiple sclerosis; Neurodegenerative diseases; Parkinson disease; Protein tyrosine kinases; Protein tyrosine phosphatases; Tyrosine phosphorylation

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Neurodegenerative diseases are chronic disorders of the CNS with diverse clinical and pathological features. Current hypotheses suggest that misfolded proteins, oxidative stress, mitochondrial dysfunction, DNA damage, neurotrophin dysfunction, and neuroinflammation play important roles in the pathogenesis of these diseases. Abnormally phosphorylated proteins, particularly those regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), are implicated in neuroinflammation and intracellular accumulation of beta-amyloid plaques and tau. Therapeutic studies targeting PTKs and PTPs provide theoretical support for future strategies in treating neurodegenerative diseases.
Neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis, are chronic disorders of the CNS that are characterized by progressive neuronal dysfunction. These diseases have diverse clinical and pathological features and their pathogenetic mechanisms are not yet fully understood. Currently, widely accepted hypotheses include the accumulation of misfolded proteins, oxidative stress from reactive oxygen species, mitochondrial dysfunction, DNA damage, neurotrophin dysfunction, and neuroinflammatory processes. In the CNS of patients with neurodegenerative diseases, a variety of abnormally phosphorylated proteins play important roles in pathological processes such as neuroinflammation and intracellular accumulation of & beta;-amyloid plaques and tau. In recent years, the roles of abnormal tyrosine phosphorylation of intracellular signaling molecules regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) in neurodegenerative diseases have attracted increasing attention. Here, we summarize the roles of signaling pathways related to protein tyrosine phosphorylation in the pathogenesis of neurodegenerative diseases and the progress of therapeutic studies targeting PTKs and PTPs that provide theoretical support for future studies on therapeutic strategies for these devastating and important neurodegenerative diseases.

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