Dendritic spine pathology in neuropsychiatric disorders

Peter Penzes*, Michael E. Cahill, Kelly A. Jones, Jon Eric Vanleeuwen, Kevin M. Woolfrey

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

889 Scopus citations

Abstract

Substantial progress has been made toward understanding the genetic architecture, cellular substrates, brain circuits and endophenotypic profiles of neuropsychiatric disorders, including autism spectrum disorders (ASD), schizophrenia and Alzheimer's disease. Recent evidence implicates spiny synapses as important substrates of pathogenesis in these disorders. Although synaptic perturbations are not the only alterations relevant for these diseases, understanding the molecular underpinnings of spine pathology may provide insight into their etiologies and may reveal new drug targets. Here we discuss recent neuropathological, genetic, molecular and animal model studies that implicate structural alterations at spiny synapses in the pathogenesis of major neurological disorders, focusing on ASD, schizophrenia and Alzheimer's disease as representatives of these categories across different ages of onset. We stress the importance of reverse translation, collaborative and multidisciplinary approaches, and the study of the spatio-temporal roles of disease molecules in the context of synaptic regulatory pathways and neuronal circuits that underlie disease endophenotypes.

Original languageEnglish (US)
Pages (from-to)285-293
Number of pages9
JournalNature neuroscience
Volume14
Issue number3
DOIs
StatePublished - Mar 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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