Calcium signaling hypothesis: A non-negligible pathogenesis in Alzheimer's disease.

BACKGROUND

Alzheimer's disease (AD) presents a significant challenge to global healthcare systems, with an exacerbation by an aging population. Although the plethora of hypotheses are proposed to elucidate the underlying mechanisms of AD, from amyloid-beta (Aβ) accumulation and Tau protein aggregation to neuroinflammation, a comprehensive understanding of its pathogenesis remains elusive. Recent research has highlighted the critical role of calcium (Ca) signaling pathway in the progression of AD, indicating a complex interplay between Ca dysregulation and various pathological processes.

AIM OF REVIEW

This review aims to consolidate the current understanding of the role of Ca signaling dysregulation in AD, thus emphasizing its central role amidst various pathological hypotheses. We aim to evaluate the potential of the Ca signaling hypothesis to unify existing theories of AD pathogenesis and explore its implications for developing innovative therapeutic strategies through targeting Ca dysregulation.

KEY SCIENTIFIC CONCEPTS OF REVIEW

The review focuses on three principal concepts. First, the indispensable role of Ca homeostasis in neuronal function and its disruption in AD. Second, the interaction between Ca signaling dysfunction and established AD hypotheses posited that Ca dysregulation is a unifying pathway. Third, the dual role of Ca in neurodegeneration and neuroprotection, highlighting the nuanced effects of Ca levels on AD pathology.