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Neuroprotective and neurorestorative potential of propargylamine derivatives in ageing: focus on mitochondrial targets

  • Translational Neurosciences - Review article
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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.

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Acknowledgments

We gratefully acknowledge the support of the Technion-Research and Development and Rappaport Family Research Institute, Technion-Israel Institute of Technology (Haifa, Israel).

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Authors and Affiliations

  1. Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, P.O.B. 9697, 31096, Haifa, Israel

    Orit Bar-Am, Tamar Amit, Moussa B. Youdim & Orly Weinreb

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  1. Orit Bar-Am
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  2. Tamar Amit
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  3. Moussa B. Youdim
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  4. Orly Weinreb
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Correspondence to Orly Weinreb.

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Bar-Am, O., Amit, T., Youdim, M.B. et al. Neuroprotective and neurorestorative potential of propargylamine derivatives in ageing: focus on mitochondrial targets. J Neural Transm 123, 125–135 (2016). https://doi.org/10.1007/s00702-015-1395-3

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  • DOI: https://doi.org/10.1007/s00702-015-1395-3

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