# SYNTHETIC MODELS OF ALZHEIMER PROTEINS

> **NIH NIH R01** · BRANDEIS UNIVERSITY · 1992 · $202,199

## Abstract

DESCRIPTION (Investigator's Abstract):  Alzheimer's disease is
characterized by three major pathologic signs:  neurofibrillary tangles
within neurons, the amyloid that surrounds and invades cerebral blood
vessels and the amyloid-rich plaques that replace degenerating nerve
terminals.  It is proposed to study the mechanism which causes the
formation of these three debilitating phenomena.  The known sequences of
cytoskeletal proteins will be compared by established homology alignment
algorithms and secondary predictive methods to search for commonality and
relatedness.  Special emphasis will be given to sequences containing
suggested phosphorylation sites and those which are rich in glutamate and
aspartate.  Fragments (5-30 residues, phosphorylated and nonphorylated) of
neurofilament (NF) and microtubule associated proteins (tau and MAP2) will
be synthesized by using solid phase and classical synthetic methods.  Their
metal ion (Ca2+, Al3+, Mg2+, Na+ and K+) binding potential and concomitant
conformational changes of these fragments, which may play a role in the
formation of the pathologies mentioned above, will be explored by physical
chemical procedures such as circular dichroism (CD) spectroscopy and CD
titration.  Molecular mechanics calculations, FTIR spectroscopy and, in
selected cases, high resolution NMR studies will be pursued to complement
CD studies.  Enzymatic phosphorylation and dephosphorylation, as well as
immunological studies, will be performed on selected peptides to test the
widespread hypothesis that aberrant phosphorylation and
hyperphosphorylation play a crucial role in the biochemistry of
neurodegenerative diseases.  Efforts will be made to find selective
chelators for Al3+ ions to prevent the binding of the neurotoxic Al3+ to
cytoskeletal proteins and delay the progress of Alzheimer's disease.

## Key facts

- **NIH application ID:** 3121957
- **Project number:** 5R01AG010002-02
- **Recipient organization:** BRANDEIS UNIVERSITY
- **SAM.gov UEI:** MXLZGAMFEKN5
- **Principal Investigator:** GERALD D FASMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $202,199
- **Award type:** 5
- **Project period:** 1991-09-30 → 1994-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121957

## Citation

> US National Institutes of Health, RePORTER application 3121957, SYNTHETIC MODELS OF ALZHEIMER PROTEINS (5R01AG010002-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121957. Licensed CC0.

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