title: Pathological stress granules in Alzheimer's disease.
abstract: A feature of neurodegenerative disease is the accumulation of insoluble protein aggregates in the brain. In some conditions, including Amyotrophic Lateral Sclerosis and Frontotemporal lobar degeneration, the primary aggregating entities are RNA binding proteins. Through regulated prion-like assembly, RNA binding proteins serve many functions in RNA metabolism that are essential for the healthy maintenance of cells of the central nervous system. Those RNA binding proteins that are the core nucleating factors of stress granules (SGs), including TIA-1, TIAR, TTP and G3BP1, are also found in the pathological lesions of other neurological conditions, such as Alzheimer's disease, where the hallmark aggregating protein is not an RNA binding protein. This discovery suggests that the regulated cellular pathway, which utilizes assembly of RNA binding proteins to package and silence mRNAs during stress, may be integral in the aberrant pathological protein aggregation that occurs in numerous neurodegenerative conditions.
authors.affiliation: Depts. of Pharmacology and Neurology, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: Peter E A
authors.initials: PE
authors.lastname: Ash
authors.affiliation: Depts. of Pharmacology and Neurology, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: Tara E
authors.initials: TE
authors.lastname: Vanderweyde
authors.affiliation: Depts. of Pharmacology and Neurology, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Youmans
authors.affiliation: Depts. of Pharmacology and Neurology, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Apicco
authors.affiliation: Depts. of Pharmacology and Neurology, Boston University School of Medicine, Boston, MA 02118, United States. Electronic address: bwolozin@bu.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wolozin
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000473:pathology*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D066263:Protein Aggregation, Pathological / Q000378:metabolism*; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D016601:RNA-Binding Proteins / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D000074019:T-Cell Intracellular Antigen-1; D051816:Tristetraprolin / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D039102:Poly(A)-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D051816:Tristetraprolin; C497552:ZFP36 protein, human; C076751:TIAL1 protein, human; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases
keywords: Alzheimer’s disease; G3BP1; Pathological stress granules; TIA-1; Tau
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