# Neuronal Calcium Signaling and Cytoskeletal Dynamics in Neurodegeneration

## TL;DR

This paper explores how calcium signaling and the cell's structural framework interact in neurons and how their disruption contributes to neurodegenerative diseases.

## Contribution

The paper provides a comprehensive review of calcium–cytoskeleton interactions and their role in neurodegeneration, emphasizing disease-specific mechanisms and therapies.

## Key findings

- Calcium-dependent cytoskeletal changes regulate synaptic plasticity and spine morphology.
- Dysregulation of calcium and cytoskeleton is linked to Alzheimer’s, Parkinson’s, and other neurodegenerative diseases.
- Emerging therapies target calcium homeostasis and cytoskeletal dynamics for treatment.

## Abstract

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.