Molecular pathology of Alzheimer neurofibrillary degeneration

• Authors: Khalid Iqbal , Alejandra Alonso , Cheng Xin Gong , Sabiha Khatoon , Takashi Kudo , Toolsee Singh , Inge Grundke-Iqbal
• Languages of publication: EN

Abstracts

EN

The most characteristic brain lesion of Alzheimer disease is the accumulation of paired helical filaments(PHF) in the affected neurons. Based on solubility in detergents there are two general populations of PHF, the readily soluble (PHF I) and the sparingly soluble (PHF II) types. The major polypeptides of PHF are the microtubule associated protein tau. Tau in PHF is present in abnormally phosphorylated forms. In addition to the PHF, the abnormal tau is also present in unpolymerized form in the AD brain. Small amounts of ubiquitin (%) are associated with PHF II but neither with PHF I nor with the unpolymerized abnormally phosphorylated tau in AD brain. Furthermore, the pretangle neurons can readily be immunolabeled for abnormally phosphorylated tau but not for ubiquitin. The level of tau in neocortex is several-fold higher than in AD aged control cases, but this increase is in the form of the abnormally phosphorylated protein. The microtubule associated proteins from AD brain do not promote the assembly of microtubules in vitro, whereas the in vitro dephosphorylated PHF polypeptides stimulate the binding of GTP to the exchangeable site of tubulin and the assembly of microtubules. In vitro the phosphate groups in PHF are less accessible than those of tau to alkaline phosphatase. It is suggested that a defect in the protein phosphorylation/dephosphorylation system leads to hyperphosphory-lation of tau. The altered tau contributes to a microtubule assembly defect and consequently compromises the axoplasmic flow and leads to neuronal degeneration.

Keywords

EN

MICROTUBULE ASSEMBLY; PROTEIN DEPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; TAU; UBIQUITINATION

Discipline

• EXPERIMENTAL_BIOLOGY_&_MEDICINE: EXPERIMENTAL BIOLOGY & MEDICINE

• Publisher: Marceli Nencki Institute of Experimental Biology, Polish Academy of Sciences
• Journal: Acta Neurobiologiae Experimentalis
• Year: 1993
• Volume: 53
• Issue: 1
• Pages: 325-335

Contributors

author

Khalid Iqbal

author

Alejandra Alonso

author

Cheng Xin Gong

author

Sabiha Khatoon

author

Takashi Kudo

author

Toolsee Singh

author

Inge Grundke-Iqbal

• Document Type: paper