Perspectives of drug-based neuroprotection targeting mitochondria.

Mitochondrial dysfunction has been reported in most neurodegenerative diseases. These anomalies include bioenergetic defect, respiratory chain-induced oxidative stress, defects of mitochondrial dynamics, increase sensitivity to apoptosis, and accumulation of damaged mitochondria with instable mitochondrial DNA. Significant progress has been made in our understanding of the pathophysiology of inherited mitochondrial disorders but most have no effective therapies. The development of new metabolic treatments will be useful not only for rare mitochondrial disorders but also for the wide spectrum of common age-related neurodegenerative diseases shown to be associated with mitochondrial dysfunction. A better understanding of the mitochondrial regulating pathways raised several promising perspectives of neuroprotection. This review focuses on the pharmacological approaches to modulate mitochondrial biogenesis, the removal of damaged mitochondria through mitophagy, scavenging free radicals and also dietary measures such as ketogenic diet.

Procaccio V ，Bris C ，Chao de la Barca JM ，Oca F ，Chevrollier A ，Amati-Bonneau P ，Bonneau D ，Reynier P ... -  《REVUE NEUROLOGIQUE》

Mitochondrial biogenesis: pharmacological approaches.

Valero T 《-》

Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders.

Islam MT 《-》

Autophagy and apoptosis dysfunction in neurodegenerative disorders.

Autophagy and apoptosis are basic physiologic processes contributing to the maintenance of cellular homeostasis. Autophagy encompasses pathways that target long-lived cytosolic proteins and damaged organelles. It involves a sequential set of events including double membrane formation, elongation, vesicle maturation and finally delivery of the targeted materials to the lysosome. Apoptotic cell death is best described through its morphology. It is characterized by cell rounding, membrane blebbing, cytoskeletal collapse, cytoplasmic condensation, and fragmentation, nuclear pyknosis, chromatin condensation/fragmentation, and formation of membrane-enveloped apoptotic bodies, that are rapidly phagocytosed by macrophages or neighboring cells. Neurodegenerative disorders are becoming increasingly prevalent, especially in the Western societies, with larger percentage of members living to an older age. They have to be seen not only as a health problem, but since they are care-intensive, they also carry a significant economic burden. Deregulation of autophagy plays a pivotal role in the etiology and/or progress of many of these diseases. Herein, we briefly review the latest findings that indicate the involvement of autophagy in neurodegenerative diseases. We provide a brief introduction to autophagy and apoptosis pathways focusing on the role of mitochondria and lysosomes. We then briefly highlight pathophysiology of common neurodegenerative disorders like Alzheimer's diseases, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Then, we describe functions of autophagy and apoptosis in brain homeostasis, especially in the context of the aforementioned disorders. Finally, we discuss different ways that autophagy and apoptosis modulation may be employed for therapeutic intervention during the maintenance of neurodegenerative disorders.

Ghavami S ，Shojaei S ，Yeganeh B ，Ande SR ，Jangamreddy JR ，Mehrpour M ，Christoffersson J ，Chaabane W ，Moghadam AR ，Kashani HH ，Hashemi M ，Owji AA ，Łos MJ ... -  《-》

Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia.

Calabrese V ，Lodi R ，Tonon C ，D'Agata V ，Sapienza M ，Scapagnini G ，Mangiameli A ，Pennisi G ，Stella AM ，Butterfield DA ... -  《JOURNAL OF THE NEUROLOGICAL SCIENCES》