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

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 (Ca²⁺) signaling pathway in the progression of AD, indicating a complex interplay between Ca²⁺ dysregulation and various pathological processes.

Aim of Review

This review aims to consolidate the current understanding of the role of Ca²⁺ signaling dysregulation in AD, thus emphasizing its central role amidst various pathological hypotheses. We aim to evaluate the potential of the Ca²⁺ signaling hypothesis to unify existing theories of AD pathogenesis and explore its implications for developing innovative therapeutic strategies through targeting Ca²⁺ dysregulation.

Key Scientific Concepts of Review

The review focuses on three principal concepts. First, the indispensable role of Ca²⁺ homeostasis in neuronal function and its disruption in AD. Second, the interaction between Ca²⁺ signaling dysfunction and established AD hypotheses posited that Ca²⁺ dysregulation is a unifying pathway. Third, the dual role of Ca²⁺ in neurodegeneration and neuroprotection, highlighting the nuanced effects of Ca²⁺ levels on AD pathology.