scholarly journals Synthetic Peptide Corresponding to The Amino-Terminal Region of the Human Tryptophanyl-Trna Synthetase, a Component Of Alzheimer’S Disease Special Congophlic Plaques AggregatesIn Vitroto Form Amyloid-Like Fibrils

2002 ◽  
Vol 2 ◽  
pp. 117-118
Author(s):  
Elena L. Paley ◽  
Vladimir Malinovskii ◽  
Beka Solomon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synthetic Peptide ◽  
Trna Synthetase ◽  
Terminal Region ◽  
Amino Terminal

scholarly journals Tau and other proteins found in Alzheimer’s disease spinal fluid are linked to retromer-mediated endosomal traffic in mice and humans

2020 ◽  
Vol 12 (571) ◽  
pp. eaba6334 ◽  
Author(s):  
Sabrina Simoes ◽  
Jessica L. Neufeld ◽  
Gallen Triana-Baltzer ◽  
Setareh Moughadam ◽  
Emily I. Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Spread ◽  
Protein Accumulation ◽  
Endosomal Trafficking ◽  
Phosphorylated Tau ◽  
Proteomic Screen ◽  
Amino Terminal ◽  
Trafficking Pathway

Endosomal trafficking has emerged as a defective biological pathway in Alzheimer’s disease (AD), and the pathway is a source of cerebrospinal fluid (CSF) protein accumulation. Nevertheless, the identity of the CSF proteins that accumulate in the setting of defects in AD’s endosomal trafficking pathway remains unknown. Here, we performed a CSF proteomic screen in mice with a neuronal-selective knockout of the core of the retromer complex VPS35, a master conductor of endosomal traffic that has been implicated in AD. We then validated three of the most relevant proteomic findings: the amino terminus of the transmembrane proteins APLP1 and CHL1, and the mid-domain of tau, which is known to be unconventionally secreted and elevated in AD. In patients with AD dementia, the concentration of amino-terminal APLP1 and CHL1 in the CSF correlated with tau and phosphorylated tau. Similar results were observed in healthy controls, where both proteins correlated with tau and phosphorylated tau and were elevated in about 70% of patients in the prodromal stages of AD. Collectively, the mouse-to-human studies suggest that retromer-dependent endosomal trafficking can regulate tau, APLP1, and CHL1 CSF concentration, informing on how AD’s trafficking pathway might contribute to disease spread and how to identify its trafficking impairments in vivo.

Comparison of amyloid from Alzheimer’s disease with synthetic peptide

Peptides ◽  
1988 ◽  
pp. 604-607
Author(s):  
Lawrence K. Duffy ◽  
Daniel A. Kirschner ◽  
Catharine L. Joachim ◽  
Alison Sinclair ◽  
Hideyo Inouye ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synthetic Peptide

SYNTHETIC PEPTIDE PROBES OF FACTOR VIII IMMUNOLOGY AND FUNCTION

1987 ◽  
Author(s):  
C A Fulcher ◽  
R A Houghten ◽  
S de Graaf Mahoney ◽  
J R Roberts ◽  
T S Zimmerman
Keyword(s):  
Amino Acid ◽  
Synthetic Peptide ◽  
Synthetic Peptides ◽  
Polyclonal Antibodies ◽  
Keyhole Limpet Hemocyanin ◽  
Significant Inhibition ◽  
Terminal Region ◽  
Amino Terminal ◽  
Microtiter Plates ◽  
Peptide Immunogen

In order to develop specific immunologic reagents for mapping functionally important sites on FVIII, we have prepared rabbit polyclonal antibodies against synthetic peptides of FVIII derived from regions along the entire FVIII amino acid sequence. To date, a total of 70 peptides have been synthesized and characterized by amino acid and HPLC analysis. The peptides were coupled to keyhole limpet hemocyanin with glutaraldehyde as a linkage reagent and used to immunize rabbits. Antisera were tested by ELISA assay on polystyrene microtiter plates coated with either the peptide immunogen, or purified FVIII. The antisera were also tested for their ability to inhibit FVIII clotting activity and to react with separated FVIII polypeptides on immunoblots.Of the 70 peptides, all reacted with the peptide immunogen, 45 reacted with purified FVIII and 33 reacted with FVIII on immunoblots. Because we had obtained evidence that cleavage of the amino terminal region of the 80 kDa polypeptide may play a role in FVIII activation by thrombin, a series of partially overlapping peptides, 15 residues in length, were synthesized in this area. After affinity purifying these antibodies on columns of FVIII immobilized on agarose, adjusting the antibodies to equal antigen binding titers by dot immunoblotting and testing for inhibition of FVIII activity, only one antibody could strongly inhibit FVIII clotting activity. This inhibition could be blocked by the peptide itself at nanomolar concentrations and no significant inhibition could be shown by antibodies to partially overlapping peptides individually, or in combination. These data suggest that a site important to FVIII function can be localized to a 15 amino acid residue region of the 80 kDa polypeptide of FVIII. In addition, a second inhibitoryantibody was identified which was produced against a peptide in the carboxy terminal region of the 54 kDa thrombin fragment of FVIII and this area is currently being studied in a similar manner. In addition, two monoclonal anti-FVIII synthetic peptide antibodies have been produced which react with purified FVIII on immunoblots. One of these antibodies also functions as an immunoadsorbent when linked to agarose and FVII can be purified in this manner, using the synthetic peptide as eluant. It is evident that antibodies to synthetic peptides of FVIII can be useful probes of FVIII structure, function and interactions as well as being of use in FVIII purification.

IC-P-029: ENHANCED BRAIN UPTAKE OF C11-PIB IN MOUSE MODEL OF ALZHEIMER'S DISEASE VIA A SYNTHETIC PEPTIDE CARRIER

2014 ◽  
Vol 10 ◽  
pp. P19-P19
Author(s):  
Val J. Lowe ◽  
Teresa Decklever ◽  
Geoffry Curran ◽  
Ann Schmeichel ◽  
Robert B. Jenkins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Synthetic Peptide ◽  
Brain Uptake ◽  
Model Of Alzheimer’S Disease ◽  
Peptide Carrier

scholarly journals The N-terminal region of non-Abeta component of Alzheimer's Disease amyloid is responsible for its tendency to assume beta-sheet and aggregate to form fibrils

1998 ◽  
Vol 258 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Omar M. A. El-Agnaf ◽  
Angela M. Bodles ◽  
David J. S. Guthrie ◽  
Patrick Harriott ◽  
G. Brent Irvine
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Terminal Region ◽  
Beta Sheet

scholarly journals Asparagine residue 368 is involved in Alzheimer's disease tau strain–specific aggregation

2020 ◽  
Vol 295 (41) ◽  
pp. 13996-14014
Author(s):  
Shotaro Shimonaka ◽  
Shin-Ei Matsumoto ◽  
Montasir Elahi ◽  
Koichi Ishiguro ◽  
Masato Hasegawa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amino Acids ◽  
Progressive Supranuclear Palsy ◽  
Corticobasal Degeneration ◽  
Terminal Region ◽  
Partial Deletion ◽  
Tau Aggregation ◽  
Asparagine Residue

In tauopathies, tau forms pathogenic fibrils with distinct conformations (termed “tau strains”) and acts as an aggregation “seed” templating the conversion of normal tau into isomorphic fibrils. Previous research showed that the aggregation core of tau fibril covers the C-terminal region (243–406 amino acids (aa)) and differs among the diseases. However, the mechanisms by which distinct fibrous structures are formed and inherited via templated aggregation are still unknown. Here, we sought to identify the key sequences of seed-dependent aggregation. To identify sequences for which deletion reduces tau aggregation, SH-SY5Y cells expressing a series of 10 partial deletion (Del 1–10, covering 244–400 aa) mutants of tau-CTF24 (243–441 aa) were treated with tau seeds prepared from a different tauopathy patient's brain (Alzheimer's disease, progressive supranuclear palsy, and corticobasal degeneration) or recombinant tau, and then seed-dependent tau aggregation was assessed biochemically. We found that the Del 8 mutant lacking 353–368 aa showed significantly decreased aggregation in both cellular and in vitro models. Furthermore, to identify the minimum sequence responsible for tau aggregation, we systematically repeated cellular tau aggregation assays for the delineation of shorter deletion sites and revealed that Asn-368 mutation suppressed tau aggregation triggered by an AD tau seed, but not using other tauopathy seeds. Our study suggested that 353–368 aa is a novel aggregation-responsible sequence other than PHF6 and PHF6*, and within this sequence, the Asn-368 residue plays a role in strain-specific tau aggregation in different tauopathies.

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