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Multiple cellular systems exist to prevent uncontrolled inflammation in brain tissues; the suppressor of cytokine signaling (SOCS) proteins have key roles in these processes. SOCS proteins are involved in restricting cellular signaling pathways by enhancing the degradation of activated receptors and removing the stimuli for continued activation. There are eight separate SOCS genes that code for proteins with similar structures and properties. All SOCS proteins can reduce signaling of activated transcription factors Janus kinase (JAK) and signal transducer and activator of transcription (STAT), but they also regulate many other signaling pathways. SOCS-1 and SOCS-3 have particular roles in regulating inflammatory processes. Chronic inflammation is a key feature of the pathology present in Alzheimer's disease (AD)-affected brains resulting from responses to amyloid plaques or neurofibrillary tangles, the pathological hallmarks of AD. The goal of this study was to examine SOCS gene expression in human non-demented (ND) and AD brains and in human brain-derived microglia to determine if AD-related pathology resulted in a deficit of these critical molecules. We demonstrated that SOCS-1, SOCS-2, SOCS-3 and cytokine-inducible SH2 containing protein (CIS) mRNA expression was increased in amyloid beta peptide (Aβ)- and inflammatory-stimulated microglia, while SOCS-6 mRNA expression was decreased by both types of treatments. Using human brain samples from the temporal cortex from ND and AD cases, SOCS-1 through SOCS-7 and CIS mRNA and SOCS-1 through SOCS-7 protein could be detected constitutively in ND and AD human brain samples. Although, the expression of key SOCS genes did not change to a large extent as a result of AD pathology, there were significantly increased levels of SOCS-2, SOCS-3 and CIS mRNA and increased protein levels of SOCS-4 and SOCS-7 in AD brains. In summary, there was no evidence of a deficit of these key inflammatory regulating proteins in aged or AD brains.
Pubmed ID: 25286386 RIS Download
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THIS RESOURCE IS NO LONGER IN SERVICE. Documented on January 4, 2023.Consortium that developed brief, standardized and reliable procedures for the evaluation and diagnosis of patients with Alzheimer's disease (AD) and other dementias of the elderly. These procedures included data forms, flipbooks, guidebooks, brochures, instruction manuals and demonstration tapes, which are now available for purchase. The CERAD assessment material can be used for research purposes as well as for patient care. CERAD has developed several basic standardized instruments, each consisting of brief forms designed to gather data on normal persons as well as on cognitively impaired or behaviorally disturbed individuals. Such data permit the identification of dementia based on clinical, neuropsychological, behavioral or neuropathological criteria. Staff at participating CERAD sites were trained and certified to administer the assessment instruments and to evaluate the subjects enrolled in the study. Cases and controls were evaluated at entry and annually thereafter including (when possible) autopsy examination of the brain to track the natural progression of AD and to obtain neuropathological confirmation of the clinical diagnosis. The CERAD database has become a major resource for research in Alzheimer's disease. It contains longitudinal data for periods as long as seven years on the natural progression of the disorder as well as information on clinical and neuropsychological changes and neuropathological manifestations.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on January 11, 2023. An autopsy-based, research-devoted brain bank, biobank and biospecimen bank that derives its human donors from the Arizona Study of Aging and Neurodegenerative Disease (AZSAND), a longitudinal clinicopathological study of the health and diseases of elderly volunteers living in Maricopa county and metropolitan Phoenix, Arizona. Their function is studied during life and their organs and tissue after death. To date, they have concentrated their studies on Alzheimer's disease, Parkinson's disease, heart disease and cancer. They share the banked tissue, biomaterials and biospecimens with qualified researchers worldwide. Registrants with suitable scientific credentials will be allowed access to a database of available tissue linked to relevant clinical information, and will allow tissue requests to be initiated.
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