Cyclosporin and mitochondria: a neuroprotective approach

Alok Singh, Vivek Khare

Abstract


Cyclosporin A (CsA) an immunophilin, discovered in 1969 and approved in 1983 to be used as immunosuppressant agent and is widely used in organ transplantation and auto-immune disorders. Its ability to alter mitochondria and apoptotic pathways makes it attractive agent to be employed in variety of diseases including age related neurodegenerative diseases. Mitochondria play pivotal role in cell energetics and reactive oxygen species production and are known to be key regulator of apoptosis hence it is important in a wide range of diseases. The structural and functional properties of mitochondria enable the targeting of drugs supposed to modulate the function of organelle for therapeutic advantage. By targeting mitochondria we can prevent oxidative damage associated with neurodegenerative diseases and ischemia and reperfusion tissue injury. Similarly targeting Bcl-2 can be helpful in cancer by triggering apoptosis.

Keywords


Cyclosporin, Mitochondria

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References


Uchino H, Elmér E, Uchino K, Lindvall O, Siesjo BK. Cyclosporin A dramatically ameliorates CA1 hippocampal damage following transient forebrain ischaemia in the rat. Acta Physiol Scand 1995;155:469-71.

Kilbaugh TJ, Bhandare S, Lorom DH, Saraswati M, Robertson CL, Margulies SS. Cyclosporin A preserves mitochondrial function after traumatic brain injury in the immature rat and piglet. J Neurotrauma 2011;28:763-74.

Leger PL, et al. Evaluation of cyclosporine A in a stroke model in the immature rat brain. Exp Neurol 2011;230:58-66.

Xie Z, et al. Neuroprotective effect of Cyclosporin A on the development of early brain injury in a subarachnoid hemorrhage model: a pilot study. Brain Res 2012;1472:113-23.

Hunt J, et al. Cylosporin A has direct effects on adult neural precursor cells. J Neurosci 2010;30:2888-96.

Hatton J, et al. Dosing and safety of cyclosporine in patients with severe brain injury. J Neurosurg 2008;109:699-707.

Neurovive Pharmaceutical AB. Project overview: cyclophilin-D-inhibiting cyclosporine-based drugs. Available at http://www.neurovive.com/Research--Development/Research-overview. Accessed 10 February 2013.