Abstract
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(2+)) signaling pathway in the progression of AD, indicating a complex interplay between Ca(2+) dysregulation and various pathological processes. AIM OF REVIEW: This review aims to consolidate the current understanding of the role of Ca(2+) signaling dysregulation in AD, thus emphasizing its central role amidst various pathological hypotheses. We aim to evaluate the potential of the Ca(2+) signaling hypothesis to unify existing theories of AD pathogenesis and explore its implications for developing innovative therapeutic strategies through targeting Ca(2+) dysregulation. KEY SCIENTIFIC CONCEPTS OF REVIEW: The review focuses on three principal concepts. First, the indispensable role of Ca(2+) homeostasis in neuronal function and its disruption in AD. Second, the interaction between Ca(2+) signaling dysfunction and established AD hypotheses posited that Ca(2+) dysregulation is a unifying pathway. Third, the dual role of Ca(2+) in neurodegeneration and neuroprotection, highlighting the nuanced effects of Ca(2+) levels on AD pathology.