title: Neuroprotective and neurorestorative potential of propargylamine derivatives in ageing: focus on mitochondrial targets.
abstract: The mitochondrial theory of ageing proposes that accumulation of damage to mitochondrial function and DNA mutation lead to ageing of humans and animals. It has been suggested that mitochondria play dynamic roles in regulating synaptogenesis and morphological/functional responses of synaptic activity, and thus, deteriorating of mitochondrial function (e.g., deficits of the mitochondrial respiratory enzymes, reduced calcium influx, increased accumulation of mitochondrial DNA defects/apoptotic proteins and impairment of mitochondrial membrane potential) can lead to severe neuronal energy deficit, and in the long run, to modifications in neuronal synapses and neurodegeneration in the ageing brain. Hence, considering the mechanisms by which mitochondrial impairment can lead to neuronal death, the development of neuroprotective molecules that target various mitochondrial pathogenic processes can be effective in the treatment of ageing and age-related neurodegenerative diseases. This review addresses several aspects of the neuroprotective effects of propargylamine derivatives (e.g., the monoamine oxidase-B inhibitors, selegiline and rasagiline and the multifunctional drugs, ladostigil, M30 and VAR10303) in ageing with a special focus on mitochondrial molecular protective mechanisms.
authors: Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, P.O.B. 9697, 31096, Haifa, Israel.
authors: Orit
authors: O
authors: Bar-Am
authors: Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, P.O.B. 9697, 31096, Haifa, Israel.
authors: Tamar
authors: T
authors: Amit
authors: Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, P.O.B. 9697, 31096, Haifa, Israel.
authors: Moussa B
authors: MB
authors: Youdim
authors: Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, P.O.B. 9697, 31096, Haifa, Israel. worly@tx.technion.ac.il.
authors: Orly
authors: O
authors: Weinreb
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010293:Pargyline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011437:Propylamines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D011437:Propylamines; C009054:propargylamine; D010293:Pargyline
keywords: Ageing brain; Mitochondrial dysfunction; Neuroprotection; Propargylamine derivatives