The p21-activated kinases in neural cytoskeletal remodeling and related neurological disorders

The serine/threonine p21-activated kinases (PAKs), as main effectors of the Rho GTPases Cdc42 and Rac, represent a group of important molecular switches linking the complex cytoskeletal networks to broad neural activity. PAKs show wide expression in the brain, but they differ in specific cell types,...

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Bibliographic Details
Published in:Protein & cell 2022-01, Vol.13 (1), p.6-25
Main Authors: Zhang, Kaifan, Wang, Yan, Fan, Tianda, Zeng, Cheng, Sun, Zhong Sheng
Format: Article
Language:English
Subjects:
Actin
Animals
Binding sites
Biochemistry
Biomedical and Life Sciences
Brain
Cdc42 protein
Cell Biology
Cell cycle
Cytoskeleton
Cytoskeleton - enzymology
Cytoskeleton - genetics
Dendritic plasticity
Dendritic spines
Developmental Biology
Developmental stages
expression pattern
Functional plasticity
Human Genetics
Humans
Kinases
Life Sciences
Morphology
Nervous system
Nervous System Diseases - enzymology
Nervous System Diseases - genetics
Neurodegenerative diseases
Neurodevelopmental disorders
Neurological diseases
Neurological disorders
neuronal function
Neurons
Neurons - enzymology
p21-activated kinases
p21-Activated Kinases - genetics
p21-Activated Kinases - metabolism
Protein Science
Proteins
Review
Signal Transduction
Stem Cells
Structure-function relationships
synaptic cytoskeletal remodeling
Therapeutic targets
Threonine
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Summary:The serine/threonine p21-activated kinases (PAKs), as main effectors of the Rho GTPases Cdc42 and Rac, represent a group of important molecular switches linking the complex cytoskeletal networks to broad neural activity. PAKs show wide expression in the brain, but they differ in specific cell types, brain regions, and developmental stages. PAKs play an essential and differential role in controlling neural cytoskeletal remodeling and are related to the development and fate of neurons as well as the structural and functional plasticity of dendritic spines. PAK-mediated actin signaling and interacting functional networks represent a common pathway frequently affected in multiple neurodevelopmental and neurodegenerative disorders. Considering specific small-molecule agonists and inhibitors for PAKs have been developed in cancer treatment, comprehensive knowledge about the role of PAKs in neural cytoskeletal remodeling will promote our understanding of the complex mechanisms underlying neurological diseases, which may also represent potential therapeutic targets of these diseases.
ISSN:1674-800X
1674-8018
DOI:10.1007/s13238-020-00812-9