Molecular Mechanisms of Alzheimer's Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy.
Level 5 - mechanism / opinion, no new human data
Narrative mechanistic review with no primary clinical or human trial data
PubMed 39851517 · doi:10.3390/cells14020089
What was done
This is a narrative review synthesizing molecular mechanisms implicated in Alzheimer's disease pathogenesis. The authors outline pathways involving amyloid precursor protein cleavage into amyloid-beta, tau phosphorylation and microtubule destabilization, microglial neuroinflammation involving NF-kappaB and NOX2-mediated reactive oxygen species, and the regulatory role of Rho GTPases (particularly RhoA) in cytoskeletal dynamics and cellular morphology.
What was found
The abstract reports no empirical numbers or quantitative findings. It describes conceptual links wherein amyloid-beta promotes tau hyperphosphorylation (leading to axonal and dendritic damage) and activates microglia to release inflammatory factors and superoxide. It also outlines how aberrant Rho GTPase regulation disrupts actin filament formation, altering neuronal processes and synaptic structures.
Why it matters
The review synthesizes classical Alzheimer's disease pathological pathways with cytoskeletal dynamics, framing RhoA/ROCK signaling as a potential target for therapeutic intervention in neurodegeneration.
Limits
As a non-systematic narrative review, the paper provides no new empirical data, quantitative synthesis, or human clinical trial results. No specific inhibitor efficacy data, dosing, or translational outcomes are reported in the abstract.
Cited by
- supports Beta-amyloid triggers both the pathological phosphorylation of tau protein and the production of reactive oxygen species in the brain.