Mitochondrion 71 (2023) 83–92 Available online 1 June 2023 1567-7249/© 2023 Elsevier B.V. and Mitochondria Research Society. All rights reserved. Review Mitochondrial dysfunction and oxidative stress in Alzheimer’s disease, and Parkinson’s disease, Huntington’s disease and Amyotrophic Lateral Sclerosis -An updated review Taha Alqahtani a, 1 , Sharada L. Deore b, 1 , Anjali A. Kide b , Bhavana A. Shende b , Ritika Sharma c , Rita Dadarao Chakole d , Lalita S. Nemade e , Nikita Kishor Kale f , Sudarshana Borah g , Savita Shrikant Deokar f , Ashok Behera h , Divya Dhawal Bhandari i , Nikita Gaikwad j , Abul Kalam Azad k, * , Arabinda Ghosh l, * a Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia b Government College of Pharmacy, Amravati, Maharastra 444604, India c University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab 140413, India d Government College of Pharmacy, Vidyanagar, Karad, Maharashtra 415124, India e Govindrao Nikam College of Pharmacy, Sawarde, Maharashtra 415606, India f PES’s Modern College of Pharmacy, Nigdi, Pune, Maharashtra 411044, India g Department of Pharmacognosy, University of Science and Technology Meghalaya Technocity, Ri-Bhoi, Meghalaya 793101, India h Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand 248009, India i University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India j Department of Pharmaceutics, P.E.S. Modern College of Pharmacy, Nigdi, Pune 411044, India k Faculty of Pharmacy, MAHSA University, Bandar Saujana Putra, Selangor 42610, Malaysia l Department of Computational Biology and Biotechnology, Mahapurusha Srimanta Sankaradeva Viswavidyalaya, Guwahati, Assam 781032, India A R T I C L E INFO Keywords: Mitochondrial dysfunction Alzheimer’s diseases Parkinson’s diseases Huntington’s diseases Amyotrophic Lateral Sclerosis ABSTRACT Misfolded proteins in the central nervous system can induce oxidative damage, which can contribute to neurodegenerative diseases in the mitochondria. Neurodegenerative patients face early mitochondrial dysfunc- tion, impacting energy utilization. Amyloid-ß and tau problems both have an effect on mitochondria, which leads to mitochondrial malfunction and, ultimately, the onset of Alzheimer’s disease. Cellular oxygen interaction yields reactive oxygen species within mitochondria, initiating oxidative damage to mitochondrial constituents. Parkinson’s disease, linked to oxidative stress, α-synuclein aggregation, and infammation, results from reduced brain mitochondria activity. Mitochondrial dynamics profoundly infuence cellular apoptosis via distinct caus- ative mechanisms. The condition known as Huntington’s disease is characterized by an expansion of polyglut- amine, primarily impacting the cerebral cortex and striatum. Research has identifed mitochondrial failure as an early pathogenic mechanism contributing to HD’s selective neurodegeneration. The mitochondria are organelles that exhibit dynamism by undergoing fragmentation and fusion processes to attain optimal bioenergetic eff- ciency. They can also be transported along microtubules and regulate intracellular calcium homeostasis through their interaction with the endoplasmic reticulum. Additionally, the mitochondria produce free radicals. The functions of eukaryotic cells, particularly in neurons, have signifcantly deviated from the traditionally assigned role of cellular energy production. Most of them are impaired in HD, which may lead to neuronal dysfunction before symptoms manifest. This article summarizes the most important changes in mitochondrial dynamics that come from neurodegenerative diseases including Alzheimer’s, Parkinson’s, Huntington’s and Amyotrophic Lateral Sclerosis. Finally, we discussed about novel techniques that can potentially treat mitochondrial mal- function and oxidative stress in four most dominating neuro disorders. * Corresponding authors. E-mail addresses: aphdukm@gmail.com (A. Kalam Azad), dra.ghosh@gauhat.ac.in, arabinda.ghosh@mssv.ac.in (A. Ghosh). 1 Equal contributing authors. Contents lists available at ScienceDirect Mitochondrion journal homepage: www.elsevier.com/locate/mito https://doi.org/10.1016/j.mito.2023.05.007 Received 26 March 2023; Received in revised form 18 May 2023; Accepted 27 May 2023