Targeting midkine and pleiotrophin signalling pathways in addiction and neurodegenerative disorders: recent progress and perspectives.

UNLABELLED: Midkine (MK) and pleiotrophin (PTN) are two neurotrophic factors that are highly up-regulated in different brain regions after the administration of various drugs of abuse and in degenerative areas of the brain. A deficiency in both MK and PTN has been suggested to be an important genetic factor, which confers vulnerability to the development of the neurodegenerative disorders associated with drugs of abuse in humans. In this review, evidence demonstrating that MK and PTN limit the rewarding effects of drugs of abuse and, potentially, prevent drug relapse is compiled. There is also convincing evidence that MK and PTN have neuroprotective effects against the neurotoxicity and development of neurodegenerative disorders induced by drugs of abuse. Exogenous administration of MK and/or PTN into the CNS by means of non-invasive methods is proposed as a novel therapeutic strategy for addictive and neurodegenerative diseases. Identification of new molecular targets downstream of the MK and PTN signalling pathways or pharmacological modulation of those already known may also provide a more traditional, but probably effective, therapeutic strategy for treating addictive and neurodegenerative disorders. LINKED ARTICLES: This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4.