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Revisiting the intersection of amyloid, pathologically modified tau and iron in Alzheimer's disease from a ferroptosis perspective.

08:00 EDT 8th October 2019 | BioPortfolio

Summary of "Revisiting the intersection of amyloid, pathologically modified tau and iron in Alzheimer's disease from a ferroptosis perspective."

The complexity of Alzheimer's disease (AD) complicates the search for effective treatments. While the key roles of pathologically modified proteins has occupied a central role in hypotheses of the pathophysiology, less attention has been paid to the potential role for transition metals overload, subsequent oxidative stress, and tissue injury. The association of transition metals, the major focus heretofore iron and amyloid, the same can now be said for the likely pathogenic microtubular associated tau (MAPT). This review discusses the interplay between iron, pathologically modified tau and oxidative stress, and connects many related discoveries. Basic principles of the transition to pathological MAPT are discussed. Iron, its homeostatic mechanisms, the recently described phenomenon of ferroptosis and purported, although still controversial roles in AD are reviewed as well as considerations to overcome existing hurdles of iron-targeted therapeutic avenues that have been attempted in AD. We summarize the involvement of multiple pathological pathways at different disease stages of disease progression that supports the potential for a combinatorial treatment strategy targeting multiple factors.

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This article was published in the following journal.

Name: Progress in neurobiology
ISSN: 1873-5118
Pages: 101716

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Medical and Biotech [MESH] Definitions

A precursor to the AMYLOID BETA-PROTEIN (beta/A4). Alterations in the expression of the amyloid beta-protein precursor (ABPP) gene, located on chromosome 21, plays a role in the development of the neuropathology common to both ALZHEIMER DISEASE and DOWN SYNDROME. ABPP is associated with the extensive extracellular matrix secreted by neuronal cells. Upon cleavage, this precursor produces three proteins of varying amino acid lengths: 695, 751, and 770. The beta/A4 (695 amino acids) or beta-amyloid protein is the principal component of the extracellular amyloid in senile plaques found in ALZHEIMER DISEASE; DOWN SYNDROME and, to a limited extent, in normal aging.

Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.

A heterogeneous group of sporadic or familial disorders characterized by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES. Clinical features include multiple, small lobar CEREBRAL HEMORRHAGE; cerebral ischemia (BRAIN ISCHEMIA); and CEREBRAL INFARCTION. Cerebral amyloid angiopathy is unrelated to generalized AMYLOIDOSIS. Amyloidogenic peptides in this condition are nearly always the same ones found in ALZHEIMER DISEASE. (from Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., 2005)

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A 4-kDa protein, 39-43 amino acids long, expressed by a gene located on chromosome 21. It is the major protein subunit of the vascular and plaque amyloid filaments in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The protein is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.

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