This review synthesizes evidence that dysregulated neuronal Ca2+-cytoskeleton interactions — including STIM/Orai-mediated store-operated calcium entry, end-binding proteins, and the spine apparatus — drive synaptic and structural pathology across neurodegenerative diseases and surveys emerging…

For Parkinson's therapeutic discovery, the paper highlights a mechanistically plausible and druggable axis (calcium–cytoskeleton) with specific molecular components to prioritize for translational studies and biomarker work, though it is a conceptual review with limited PD-specific experimental or…

Neuronal function relies on the precise coordination between intracellular calcium (Ca2+) signaling and the cytoskeletal architecture that underpins synaptic transmission, plasticity, and structural stability. Disruption of this calcium-cytoskeleton interplay has been noted in numerous neurodegenerative diseases. We discuss how Ca2+-dependent cytoskeletal remodeling governs long-term potentiation and depression, dendritic spine morphology, and presynaptic function, highlighting the functions of end-binding proteins, STIM (Stromal Interaction Molecule)/Orai-mediated store-operated calcium entry, and the spine apparatus. Disease-specific manifestations of cytoskeletal-calcium dysregulation are reviewed across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, tauopathies, and prion disorders. Finally, we evaluate emerging therapeutic strategies targeting calcium homeostasis, cytoskeletal dynamics, and their downstream effectors, including multi-target approaches.