Publication: The pathophysiology of triose phosphate isomerase dysfunction in Alzheimer’s disease
Authors
Tajes, Marta ; Guivernau, Biuse ; Ramos Fernández, Eva ; Bosch Morató, Mónica ; Palomer, Ernest ; Guix, Francesc X. ; Muñoz, Francisco J.
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Alzheimer’s disease (AD), the most
prevalent neurodegenerative disease worldwide, has two
main hallmarks: extracellular deposits of amyloid ß-
peptide (Aß) and intracellular neurofibrillary tangles
composed by tau protein. Most AD cases are sporadic
and are not dependent on known genetic causes; aging is
the major risk factor for AD. Therefore, the oxidative
stress has been proposed to initiate the uncontrolled
increase in Aß production and also to mediate the Aß’s
deleterious effects on brain cells, especially on neurons
from the cortex and hippocampus. The production of
free radicals in the presence of nitric oxide (NO) yields
to the peroxynitrite generation, a very reactive agent that
nitrotyrosinates the proteins irreversibly. The
nitrotyrosination produces a loss of protein physiological
functions, contributing to accelerate AD progression.
One of the most nitrotyrosinated proteins in AD is the
enzyme triosephosphate isomerase (TPI) that isomerises
trioses, regulating glucose consumption by both
phosphate pentose and glycolytic pathways and thereby
pyruvate production. Hence, any disturbance in the
glucose supply could affect the proper brain function,
considering that the brain has a high rate of glucose
consumption. Besides this directly affecting to the
energetic metabolism of the neurons, TPI modifications,
such as mutation or nitrotyrosination, increase
methylglyoxal production, a toxic precursor of advanced
glycated end-products (AGEs) and responsible for
protein glycation. Moreover, nitro-TPI aggregates
interact with tau protein inducing the intraneuronal
aggregation of tau. Here we review the relationship
between modified TPI and AD, highlighting the
relevance of this protein in AD pathology and the
consequences of protein nitro-oxidative modifications.
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Citation
Histology and histopathology, Vol. 28, n.º 1 (2013)
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