Mitochondrial fission and fusion in neurodegenerative diseases:Ca2+ signalling

Abstract

Neurodegenerative diseases (NDs) are a group of disorders characterized by the progressive loss of neuronal structure and function. The pathogenesis is intricate and involves a network of interactions among multiple causes and systems. Mitochondria and Ca²⁺ signaling have long been considered to play important roles in the development of various NDs. Mitochondrial fission and fusion dynamics are important processes of mitochondrial quality control, ensuring the stability of mitochondrial structure and function. Mitochondrial fission and fusion imbalance and Ca²⁺ signaling disorders can aggravate the disease progression of NDs. In this review, we explore the relationship between mitochondrial dynamics and Ca²⁺ signaling in AD, PD, ALS, and HD, focusing on the roles of key regulatory proteins (Drp1, Fis1, Mfn1/2, and Opa1) and the association structures between mitochondria and the endoplasmic reticulum (MERCs/MAMs). We provide a detailed analysis of their involvement in the pathogenesis of these four NDs. By integrating these mechanisms, we aim to clarify their contributions to disease progression and offer insights into the development of therapeutic strategies that target mitochondrial dynamics and Ca²⁺ signaling. We also examine the progress in drug research targeting these pathways, highlighting their potential as therapeutic targets in the treatment of NDs.