Proteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression

Behan, Á T; Byrne, C.J.; Dünn, Michael J.; Cagney, Gerard; Cotter, David

doi:10.1038/mp.2008.7

Cited by 155 publications

(138 citation statements)

References 87 publications

(94 reference statements)

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“…The authors concluded that a PSD fraction can be isolated from human postmortem brain tissues with a reasonable degree of integrity (Hahn et al, 2009). Another group has used high-speed centrifugation, detergents, and sucrose gradients to isolate a 'detergentresistant membrane fraction' that they refer to as membrane microdomains (Behan et al, 2009;Parkin et al, 1999).…”

Section: Biochemical Enrichment Of Postsynaptic Densitiesmentioning

confidence: 99%

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

McCullumsmith

Hammond

Shan

et al. 2013

Neuropsychopharmacol

102

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We propose that postmortem tissue is an underutilized substrate that may be used to translate genetic and/or preclinical studies, particularly for neuropsychiatric illnesses with complex etiologies. Postmortem brain tissues from subjects with schizophrenia have been extensively studied, and thus serve as a useful vehicle for illustrating the challenges associated with this biological substrate. Schizophrenia is likely caused by a combination of genetic risk and environmental factors that combine to create a disease phenotype that is typically not apparent until late adolescence. The complexity of this illness creates challenges for hypothesis testing aimed at understanding the pathophysiology of the illness, as postmortem brain tissues collected from individuals with schizophrenia reflect neuroplastic changes from a lifetime of severe mental illness, as well as treatment with antipsychotic medications. While there are significant challenges with studying postmortem brain, such as the postmortem interval, it confers a translational element that is difficult to recapitulate in animal models. On the other hand, data derived from animal models typically provide specific mechanistic and behavioral measures that cannot be generated using human subjects. Convergence of these two approaches has led to important insights for understanding molecular deficits and their causes in this illness. In this review, we discuss the problem of schizophrenia, review the common challenges related to postmortem studies, discuss the application of biochemical approaches to this substrate, and present examples of postmortem schizophrenia studies that illustrate the role of the postmortem approach for generating important new leads for understanding the pathophysiology of severe mental illness.

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Section: Biochemical Enrichment Of Postsynaptic Densitiesmentioning

confidence: 99%

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

McCullumsmith

Hammond

Shan

et al. 2013

Neuropsychopharmacol

102

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“…In axon terminals, CME proteins mediate the incorporation of proteins such as SNARE proteins, into synaptic vesicles, thereby indirectly modulating their functional properties 61 . SNAREs are crucial for synaptic vesicle fusion and exocytosis, and SNARE-related abnormalities are well documented in psychosis 56, [90][91][92] . These functions, as mentioned earlier, are mediated by BLOC-1, another constituent of clathrin coated vesicles.…”

Section: Altered Cme May Contribute To Synaptic Pathologymentioning

confidence: 99%

Hypothesis review: are clathrin-mediated endocytosis and clathrin-dependent membrane and protein trafficking core pathophysiological processes in schizophrenia and bipolar disorder?

et al. 2011

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Clathrin mediated endocytosis (CME) is the best characterized mechanism governing cellular membrane-and protein trafficking. In this hypothesis review, we integrate recent evidence implicating CME and related cellular trafficking mechanisms in the pathophysiology of psychotic disorders such as schizophrenia and bipolar disorder. The evidence includes proteomic and genomic findings implicating proteins and genes of the CME interactome. Additionally, several important candidate genes for schizophrenia, such as dysbindin, are involved in processes closely linked to CME and membrane trafficking. We discuss that key aspects of psychosis neuropathology such as synaptic dysfunction, white matter changes, and aberrant neurodevelopment are all influenced by CME, and that other cellular trafficking mechanisms previously linked to psychoses interact with CME in important ways. Furthermore, many antipsychotic drugs have been shown to affect clathrin-interacting proteins. We propose that the targeted pharmacological manipulation of CME may offer fruitful opportunities for novel treatments of schizophrenia.

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“…[50][51][52][53] They have demonstrated alterations in cytoskeletal, synaptic, metabolic, and mitochondrial proteins. 42,[44][45][46]48,50,54 To our knowledge, with regard to the hippocampus, there has been 1 previous proteomic study in schizophrenia 54 and none in bipolar disorder.…”

mentioning

confidence: 99%

“…37 Usingproteomicmethods, it is possible to assess global differential protein expression between disease and control states and to obtain novel insights into disease (for reviews, see the articles by English etal, 38 Görgetal, 39 andTannuandHemby 40 ).Proteomicstudies of postmortem brain tissue from subjects with schizophrenia and from subjects with bipolar disorder have focused largely on the dorsolateral prefrontal cortex [41][42][43][44][45][46][47][48][49] and the anterior cingulate cortex. [50][51][52][53] They have demonstrated alterations in cytoskeletal, synaptic, metabolic, and mitochondrial proteins.…”

mentioning

confidence: 99%