Alpha-synuclein and chaperones in dementia with Lewy bodies. 2005

Ippolita Cantuti-Castelvetri, and Jochen Klucken, and Martin Ingelsson, and Karunya Ramasamy, and Pamela J McLean, and Matthew P Frosch, and Bradley T Hyman, and David G Standaert
Massachusetts General Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.

The protein alpha-synuclein (ASYN) is thought to be involved in the development of dementia with Lewy bodies (DLB). Overexpression of ASYN has been linked to cellular toxicity and human disease, and in experimental models, chaperones such as heat shock proteins (HSPs) are protective against ASYN toxicity. We have assessed the abundance of mRNA for ASYN and chaperones and the abundance and solubility of the encoded proteins in temporal cortex from sporadic human DLB. We found a reduction of ASYN mRNA in DLB (44.9% of control). The abundance of the Triton-soluble fraction (bioavailable protein) was not altered, but there was an increase of the Triton-insoluble component (likely representing aggregates). We evaluated 3 chaperones: HSP70, HSP90, and HDJ1. HSP70 mRNA was increased in DLB, whereas the mRNAs for HSP90 and HDJ1 were unchanged. HSP70 accumulated in the Triton-soluble fraction, whereas HSP90 and HDJ1 proteins accumulated in the Triton-insoluble fraction. These observations suggest that sporadic DLB is not associated with overexpression of ASYN. Rather, the persistence of normal soluble ASYN protein levels, despite the reduction of its mRNA, suggests a primary defect in clearance of the protein. However, this reduced clearance cannot be attributed to a failure of chaperone expression, because their mRNA is unchanged or increased in the DLB brain.

UI MeSH Term Description Entries
D003902 Detergents Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. Cleansing Agents,Detergent Pods,Laundry Detergent Pods,Laundry Pods,Syndet,Synthetic Detergent,Agent, Cleansing,Agents, Cleansing,Cleansing Agent,Detergent,Detergent Pod,Detergent Pod, Laundry,Detergent Pods, Laundry,Detergent, Synthetic,Detergents, Synthetic,Laundry Detergent Pod,Laundry Pod,Pod, Detergent,Pod, Laundry,Pod, Laundry Detergent,Pods, Detergent,Pods, Laundry,Pods, Laundry Detergent,Synthetic Detergents
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012995 Solubility The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Solubilities
D013702 Temporal Lobe Lower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the OCCIPITAL LOBE. Anterior Temporal Lobe,Brodmann Area 20,Brodmann Area 21,Brodmann Area 22,Brodmann Area 37,Brodmann Area 38,Brodmann Area 52,Brodmann's Area 20,Brodmann's Area 21,Brodmann's Area 22,Brodmann's Area 37,Brodmann's Area 38,Brodmann's Area 52,Inferior Temporal Gyrus,Middle Temporal Gyrus,Parainsular Area,Fusiform Gyrus,Gyrus Fusiformis,Gyrus Temporalis Superior,Inferior Horn of Lateral Ventricle,Inferior Horn of the Lateral Ventricle,Lateral Occipito-Temporal Gyrus,Lateral Occipitotemporal Gyrus,Occipitotemporal Gyrus,Planum Polare,Superior Temporal Gyrus,Temporal Cortex,Temporal Gyrus,Temporal Horn,Temporal Horn of the Lateral Ventricle,Temporal Operculum,Temporal Region,Temporal Sulcus,Anterior Temporal Lobes,Area 20, Brodmann,Area 20, Brodmann's,Area 21, Brodmann,Area 21, Brodmann's,Area 22, Brodmann,Area 22, Brodmann's,Area 37, Brodmann,Area 37, Brodmann's,Area 38, Brodmann,Area 38, Brodmann's,Area 52, Brodmann,Area 52, Brodmann's,Area, Parainsular,Areas, Parainsular,Brodmanns Area 20,Brodmanns Area 21,Brodmanns Area 22,Brodmanns Area 37,Brodmanns Area 38,Brodmanns Area 52,Cortex, Temporal,Gyrus, Fusiform,Gyrus, Inferior Temporal,Gyrus, Lateral Occipito-Temporal,Gyrus, Lateral Occipitotemporal,Gyrus, Middle Temporal,Gyrus, Occipitotemporal,Gyrus, Superior Temporal,Gyrus, Temporal,Horn, Temporal,Lateral Occipito Temporal Gyrus,Lobe, Anterior Temporal,Lobe, Temporal,Occipito-Temporal Gyrus, Lateral,Occipitotemporal Gyrus, Lateral,Operculum, Temporal,Parainsular Areas,Region, Temporal,Sulcus, Temporal,Temporal Cortices,Temporal Gyrus, Inferior,Temporal Gyrus, Middle,Temporal Gyrus, Superior,Temporal Horns,Temporal Lobe, Anterior,Temporal Lobes,Temporal Lobes, Anterior,Temporal Regions
D016022 Case-Control Studies Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time. Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control
D016133 Polymerase Chain Reaction In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain
D050956 HSP40 Heat-Shock Proteins A family of heat-shock proteins that contain a 70 amino-acid consensus sequence known as the J domain. The J domain of HSP40 heat shock proteins interacts with HSP70 HEAT-SHOCK PROTEINS. HSP40 heat-shock proteins play a role in regulating the ADENOSINE TRIPHOSPHATASES activity of HSP70 heat-shock proteins. DnaJ Protein,HSP40 Heat-Shock Protein,HSP40 Protein,Heat-Shock Proteins 40,DnaJ Proteins,HSP40 Protein Family,HSP40 Proteins,Heat Shock Protein 40 Family,Heat-Shock Protein 40,HSP40 Heat Shock Protein,HSP40 Heat Shock Proteins,Heat Shock Protein 40,Heat Shock Proteins 40,Heat-Shock Protein, HSP40,Heat-Shock Proteins, HSP40,Protein, DnaJ,Protein, HSP40,Protein, HSP40 Heat-Shock,Proteins, HSP40 Heat-Shock
D051844 alpha-Synuclein A synuclein that is a major component of LEWY BODIES and plays a role in SYNUCLEINOPATHIES, neurodegeneration and neuroprotection. Non-AB Component of AD Amyloid Protein,Non AB Component of AD Amyloid Protein,alpha Synuclein
D017830 Octoxynol Nonionic surfactant mixtures varying in the number of repeating ethoxy (oxy-1,2-ethanediyl) groups. They are used as detergents, emulsifiers, wetting agents, defoaming agents, etc. Octoxynol-9, the compound with 9 repeating ethoxy groups, is a spermatocide. Octylphenoxypolyethoxyethanols,Octoxinol,Octoxinols,Octoxynol-9,Octoxynols,Octylphenoxy Polyethoxyethanol,Triton X-100,Triton X-305,Triton X-45,Octoxynol 9,Polyethoxyethanol, Octylphenoxy,Triton X 100,Triton X 305,Triton X 45,Triton X100,Triton X305,Triton X45

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