title: Cyclophilin-D inhibition in neuroprotection: dawn of a new era of mitochondrial medicine.
abstract: Traumatic brain injury and ischemia can result in marked neuronal degeneration and residual impairment of cerebral function. However, no effective pharmacological treatment directed at tissues of the central nervous system (CNS) for acute intervention has been developed. The detailed pathophysiological cascade leading to -neurodegeneration in these conditions has not been elucidated, but cellular calcium overload and mitochondrial dysfunction have been implicated in a wide range of animal models involving degeneration of the CNS. In particular, activation of the calcium-induced mitochondrial permeability transition (mPT) is considered to be a major cause of cell death inferred by the broad and potent neuroprotective effects of -pharmacological inhibitors of mPT, especially modulators of cyclophilin activity and, more specifically, genetic inactivation of the mitochondrial cyclophilin, cyclophilin D. Reviewed are evidence and challenges that could bring on the dawning of mitochondrial medicine aimed at safeguarding energy supply following acute injury to the CNS.
authors.affiliation: Department of Anesthesiology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan. h-uchi@tokyo-med.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchino
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hatakeyama
authors.forename: Saori
authors.initials: S
authors.lastname: Morota
authors.forename: Tadashi
authors.initials: T
authors.lastname: Tanoue
authors.forename: Takahisa
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Daiki
authors.initials: D
authors.lastname: Usui
authors.forename: Chisato
authors.initials: C
authors.lastname: Taguchi
authors.forename: Morika
authors.initials: M
authors.lastname: Suzuki
authors.forename: Magnus J
authors.initials: MJ
authors.lastname: Hansson
authors.forename: Eskil
authors.initials: E
authors.lastname: Elmér
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000494:pharmacology / Q000627:therapeutic use; D001930:Brain Injuries / Q000188:drug therapy; D002118:Calcium / Q000378:metabolism; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007511:Ischemia / Q000188:drug therapy; D008928:Mitochondria / Q000187:drug effects*; D018696:Neuroprotective Agents
chemical_list: D001152:Arsenicals; D000081406:Peptidyl-Prolyl Isomerase F; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; C029341:oxophenylarsine; D016572:Cyclosporine; D021983:Cyclophilins; D002118:Calcium