TY - JOUR
T1 - Dendritic spine pathology in neuropsychiatric disorders
AU - Penzes, Peter
AU - Cahill, Michael E.
AU - Jones, Kelly A.
AU - Vanleeuwen, Jon Eric
AU - Woolfrey, Kevin M.
PY - 2011/3/1
Y1 - 2011/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79951960867&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951960867&partnerID=8YFLogxK
U2 - 10.1038/nn.2741
DO - 10.1038/nn.2741
M3 - Review article
C2 - 21346746
AN - SCOPUS:79951960867
VL - 14
SP - 285
EP - 293
JO - Nature Neuroscience
JF - Nature Neuroscience
SN - 1097-6256
IS - 3
ER -