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Proteomes 2018, 6(4), 46; https://doi.org/10.3390/proteomes6040046

Deep Profiling of the Aggregated Proteome in Alzheimer’s Disease: From Pathology to Disease Mechanisms

Departments of Structural Biology and Developmental Neurobiology, Center for Proteomics and Metabolomics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
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Received: 22 September 2018 / Revised: 29 October 2018 / Accepted: 7 November 2018 / Published: 12 November 2018
(This article belongs to the Special Issue Neuroproteomics)
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Abstract

Hallmarks of Alzheimer’s disease (AD), a progressive neurodegenerative disease causing dementia, include protein aggregates such as amyloid beta plaques and tau neurofibrillary tangles in a patient’s brain. Understanding the complete composition and structure of protein aggregates in AD can shed light on the as-yet unidentified underlying mechanisms of AD development and progression. Biochemical isolation of aggregates coupled with mass spectrometry (MS) provides a comprehensive proteomic analysis of aggregates in AD. Dissection of these AD-specific aggregate components, such as U1 small nuclear ribonucleoprotein complex (U1 snRNP), provides novel insights into the deregulation of RNA splicing in the disease. In this review, we summarize the methodologies of laser capture microdissection (LCM) and differential extraction to analyze the aggregated proteomes in AD samples, and discuss the derived novel insights that may contribute to AD pathogenesis. View Full-Text
Keywords: proteomics; proteome; mass spectrometry; Alzheimer’s disease; protein aggregation; laser capture microdissection; splicing; U1 snRNP proteomics; proteome; mass spectrometry; Alzheimer’s disease; protein aggregation; laser capture microdissection; splicing; U1 snRNP
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Lutz, B.M.; Peng, J. Deep Profiling of the Aggregated Proteome in Alzheimer’s Disease: From Pathology to Disease Mechanisms. Proteomes 2018, 6, 46.

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