Elsevier, Behavioural Brain Research, Volume 414, 24 September 2021
Rho-associated coiled-coil kinase (ROCK), a serine/threonine kinase regulated by the small GTPase RhoA, is involved in regulating cell migration, proliferation, and survival. Numerous studies have shown that the RhoA/ROCK signaling pathway can promote Alzheimer's disease (AD) occurrence. ROCK activation increases β-secretase activity and promotes amyloid-beta (Aβ) production; moreover, Aβ further activates ROCK. This is suggestive of a possible positive feedback role for Aβ and ROCK. Moreover, ROCK activation promotes the formation of neurofibrillary tangles and abnormal synaptic contraction. Additionally, ROCK activation can promote the neuroinflammatory response by activating microglia and astrocytes to release inflammatory cytokines. Therefore, ROCK is a promising drug target in AD; further, there is a need to elucidate the specific mechanism of action.
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Keywords:
Alzheimer Disease; Alzheimer's Disease; Amino Acid Sequence; Amyloid Beta Protein; Amyloid Beta-Peptides; Amyloid-β; Animal; Animals; Apoptosis; Aspartic Proteinase; Astrocyte; Biofilm; Cell Proliferation; Chromosome 17; Cognition; Cyclin Dependent Kinase 5; Cytotoxicity; Enzyme Activity; Human; Humans; Inducible Nitric Oxide Synthase; Inflammasome; Innate Immunity; Intrinsically Disordered Protein; Long Term Depression; MAPT Protein, Human; Metabolism; Morphogenesis; Nerve Degeneration; Nervous System Inflammation; Neuroinflammation; Neuroinflammatory Diseases; Neuroprotection; Nitric Oxide; Nonhuman; Nonsteroid Antiinflammatory Agent; Oligodendroglia; Phagocytosis; Phosphatidylinositol 3 Kinase; Pleckstrin Homology Domain; Protein Phosphorylation; Protein Serine Threonine Kinase; RHOA Protein, Human; Review; Rho Kinase; Rho-Associated Kinases; RhoA GTP-Binding Protein; RhoA Guanine Nucleotide Binding Protein; RhoB Guanine Nucleotide Binding Protein; RhoC Guanine Nucleotide Binding Protein; Serine; Signal Transduction; Tau; Tau Protein; Tau Proteins; Global