Advanced glycation end products and neurodegenerative diseases: Mechanisms and perspective

Li, Jinlong; Liu, Danian; Sun, Ling; Lu, Yunting; Zhang, Zhongling

doi:10.1016/j.jns.2012.02.018

Cited by 264 publications

(186 citation statements)

References 49 publications

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“…T h e m e c h a n i s m l e a d i n g n o r m a l t a u t o b e c o m e hyperphosphorylated remains unknown and posttranslational modifications besides phosphorylation could regulate tau function and aggregation [58] , such as ubiquitination [59] , glycation [60] , glycosylation [61] , nitration [62] , polyamination [63] , proteolysis [64] , acetylation [58] , and methylation [65] .…”

Section: Other Post-translational Modifi Cationsmentioning

confidence: 99%

Tau-induced neurodegeneration: mechanisms and targets

Beharry

Cohen

et al. 2014

Neurosci. Bull.

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The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau's functions in microtubule assembly and stabilization and with regard to its interactions with other proteins. We describe and analyze important post-translational modifications: hyperphosphorylation, ubiquitination, glycation, glycosylation, nitration, polyamination, proteolysis, acetylation, and methylation. We discuss how these post-translational modifi cations can alter tau's biological function. We analyze the role of mitochondrial health in neurodegeneration. We propose that microtubules could be a therapeutic target and review different approaches. Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and propose a mechanism of neurodegeneration.Keywords: tau; phosphorylation; neurodegeneration; tauopathies; mitochondria; microtubules; tubulin; kinases; phosphatases; Alzheimer's disease ·Review· IntroductionAlzheimer 's disease (AD), first described by Alois Alzheimer more than 100 years ago [1] , is a progressive neurodegenerative disorder, characterized by an insidious onset with irreversible cognitive declines that lead to profound mental deterioration causing dementia [2] . Two major forms of lesion characterize AD: amyloid as diffuse neurotic plaques primarily composed of the Aβ peptide [3] , which are mainly insoluble deposits of protein and cellular material, and neurofibrillary tangles composed of fi lamentous hyperphosphorylated tau protein that builds up inside the neuron [4,5] .Amyloid precursor protein (APP) is a highly conserved transmembrane protein [6] believed to play a role in synapse formation, synaptic plasticity, and neuronal survival [7][8][9] .In AD, APP is cleaved by β-and γ-secretases leading to the overproduction of an abnormal proteolytic byproduct called amyloid beta (Aβ) [10] . Upon cleavage fragments of Aβ of various sizes are released from the membrane and aggregate in the brain to form the characteristic plaques seen in AD. Plaques are composed primarily of the 40 and 42 amino-acid peptide fragments Aβ40 and Aβ42, the latter being the predominant species. In addition, Aβ42 is more prone to aggregation and deposition and therefore the cause of neurotoxicity, as well as synaptic loss [11] .The second lesion in AD is formed by aggregates of the microtubule-associated protein tau, which forms intracytoplasmic neuronal inclusions or neurofibrillary tangles when hyperphosphorylated [12] . Tau is associated with neurons of the central nervous system [13] and its main biological function is promoting the in vitro assembly and stabilization of microtubules in the cytoskeleton [14,15] . Tau is a phosphoprotein that is encoded by a single gene, MAPT, located on chromosome 17q21 [16] ; alternative splicing of the gene produces six major isoforms expressed in the adult human brain [17] . Isoforms derive their names from the number of microtubule-binding repeat s...

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Section: Other Post-translational Modifi Cationsmentioning

confidence: 99%

Tau-induced neurodegeneration: mechanisms and targets

Beharry

Cohen

et al. 2014

Neurosci. Bull.

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“…The ultimate amount of ROS/RNS is under strict control in the body as a result of enzymatic and non-enzymatic defense mechanisms. The production of ROS-and RNS-induced damage (the final effect of OS) in tissue can be confirmed by the presence of tissue-specific and non-specific biomarkers [15][16][17][18][19][20]. Several markers of OS and antioxidant activity are presented in Fig.…”

Section: Introductionmentioning

confidence: 82%

Oxidative Stress in Neurodegenerative Diseases

Xueping¹,

Chen²,

Chunyan³

et al. 2013

Metal‐based Neurodegeneration

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“…AGEs are considered to induce the development or support the progression of neurodegenerative diseases and their toxic properties are known to stem from oxidative stress and inflammation [48,49]. AGEs localize in senile plaques and extracellular spaces in AD [50][51][52] and AGE-albumin and RAGE binding stimulate the activations of diverse signaling cascades through MAPK (mitogen-activated protein kinases) and bcl-2-like protein 4 (Bax) pathways that result in neuron apoptosis [29].…”

Section: Advanced Glycation End Products (Ages)mentioning

confidence: 99%