非表示:
キーワード:
Neuroimmunophilin, FKBP51, FK506, Neurite outgrowth, Stress-related disorders
要旨:
Background: Ligands for FK506-binding proteins, also referred to as
neuroimmunophilin ligands, have repeatedly been described as
neuritotrophic, neuroprotective or neuroregenerative agents. However,
the precise molecular mechanism of action underlying the observed
effects has remained elusive, which eventually led to a reduced interest
in FKBP ligand development.
Scope of review: A survey is presented on the pharmacology of
neuroimmunophilin ligands, of the current understanding of individual
FKBP homologs in neuronal processes and an assessment of their potential
as drug targets for CNS disorders.
Major conclusions: FKBP51 is the major target accounting for the
neuritotrophic effect of neuroimmunophilin ligands. Selectivity against
the homolog FKBP52 is essential for optimal neuritotrophic efficacy.
General significance: Selectivity within the FKBP family, in particular
selective inhibition of FKBP12 or FKBP51, is possible. FKBP51 is a
pharmacologically tractable target for stress-related disorders. The
role of FKBPs in neurodegeneration remains to be clarified. This article
is part of a Special Issue entitled Proline-directed Foldases: Cell
Signaling Catalysts and Drug Targets. (C) 2015 Elsevier B.V. All rights
reserved.
