Mitochondrial Crosstalk in Neurodegeneration: Mechanistic Pathways, Quality Control, and Therapeutic Perspectives

A growing number of people around the world are suffering from neurodegenerative disorders, which cause a slow but steady decline in brain function. Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Parkinson's disease (HD) all share similar molecular pathologies despite their clinically variable symptoms. Mitochondrial dysfunction is a hallmark of central nervous system neurodegenerative diseases. Impaired communication between mitochondria and other organelles may play a crucial role in neurodegeneration, as has been shown by the development of better technology, more advanced imaging techniques, and animal models. Essential for neuronal survival, this intricate inter-organelle communication network controls inflammatory responses, mitochondrial quality, redox balance, calcium homeostasis, and energy metabolism. Dysregulation of mitochondrial crosstalk is associated with oxidative stress, defective mitophagy, altered calcium metabolism and chronic neuroinflammation that ultimately potentiate neuronal degeneration. This mechanistic dissection reveals the molecular cascades that control mitochondrial talking to nucleus, endoplasmic reticulum (ER), lysosome and immune system signaling in neurodegeneration. Furthermore, it highlights disease-specific alterations in mitochondrial communication as well as new avenues for treating neurodegenerative disorders that aim to intervene with mitochondrial communication networks as possible treatments for disease modification. To better understand the mechanisms underlying neurodegenerative illnesses and to create new therapeutic techniques that target mitochondria, it is important to understand how mitochondria interact inside and between cells.