Disruption of neuronal autophagy by infected microglia results in neurodegeneration.

There is compelling evidence to support the idea that autophagy has a protective function in neurons and its disruption results in neurodegenerative disorders. Neuronal damage is well-documented in the brains of HIV-infected individuals, and evidence of inflammation, oxidative stress, damage to syna...

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Autores principales:	Mehrdad Alirezaei, William B Kiosses, Claudia T Flynn, Nathan R Brady, Howard S Fox
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/56019c7dd51c4684b54b36e56a5dad79
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spelling	oai:doaj.org-article:56019c7dd51c4684b54b36e56a5dad792021-11-25T06:11:17ZDisruption of neuronal autophagy by infected microglia results in neurodegeneration.1932-620310.1371/journal.pone.0002906https://doaj.org/article/56019c7dd51c4684b54b36e56a5dad792008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18682838/?tool=EBIhttps://doaj.org/toc/1932-6203There is compelling evidence to support the idea that autophagy has a protective function in neurons and its disruption results in neurodegenerative disorders. Neuronal damage is well-documented in the brains of HIV-infected individuals, and evidence of inflammation, oxidative stress, damage to synaptic and dendritic structures, and neuronal loss are present in the brains of those with HIV-associated dementia. We investigated the role of autophagy in microglia-induced neurotoxicity in primary rodent neurons, primate and human models. We demonstrate here that products of simian immunodeficiency virus (SIV)-infected microglia inhibit neuronal autophagy, resulting in decreased neuronal survival. Quantitative analysis of autophagy vacuole numbers in rat primary neurons revealed a striking loss from the processes. Assessment of multiple biochemical markers of autophagic activity confirmed the inhibition of autophagy in neurons. Importantly, autophagy could be induced in neurons through rapamycin treatment, and such treatment conferred significant protection to neurons. Two major mediators of HIV-induced neurotoxicity, tumor necrosis factor-alpha and glutamate, had similar effects on reducing autophagy in neurons. The mRNA level of p62 was increased in the brain in SIV encephalitis and as well as in brains from individuals with HIV dementia, and abnormal neuronal p62 dot structures immunoreactivity was present and had a similar pattern with abnormal ubiquitinylated proteins. Taken together, these results identify that induction of deficits in autophagy is a significant mechanism for neurodegenerative processes that arise from glial, as opposed to neuronal, sources, and that the maintenance of autophagy may have a pivotal role in neuroprotection in the setting of HIV infection.Mehrdad AlirezaeiWilliam B KiossesClaudia T FlynnNathan R BradyHoward S FoxPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 8, p e2906 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mehrdad Alirezaei William B Kiosses Claudia T Flynn Nathan R Brady Howard S Fox Disruption of neuronal autophagy by infected microglia results in neurodegeneration.
description	There is compelling evidence to support the idea that autophagy has a protective function in neurons and its disruption results in neurodegenerative disorders. Neuronal damage is well-documented in the brains of HIV-infected individuals, and evidence of inflammation, oxidative stress, damage to synaptic and dendritic structures, and neuronal loss are present in the brains of those with HIV-associated dementia. We investigated the role of autophagy in microglia-induced neurotoxicity in primary rodent neurons, primate and human models. We demonstrate here that products of simian immunodeficiency virus (SIV)-infected microglia inhibit neuronal autophagy, resulting in decreased neuronal survival. Quantitative analysis of autophagy vacuole numbers in rat primary neurons revealed a striking loss from the processes. Assessment of multiple biochemical markers of autophagic activity confirmed the inhibition of autophagy in neurons. Importantly, autophagy could be induced in neurons through rapamycin treatment, and such treatment conferred significant protection to neurons. Two major mediators of HIV-induced neurotoxicity, tumor necrosis factor-alpha and glutamate, had similar effects on reducing autophagy in neurons. The mRNA level of p62 was increased in the brain in SIV encephalitis and as well as in brains from individuals with HIV dementia, and abnormal neuronal p62 dot structures immunoreactivity was present and had a similar pattern with abnormal ubiquitinylated proteins. Taken together, these results identify that induction of deficits in autophagy is a significant mechanism for neurodegenerative processes that arise from glial, as opposed to neuronal, sources, and that the maintenance of autophagy may have a pivotal role in neuroprotection in the setting of HIV infection.
format	article
author	Mehrdad Alirezaei William B Kiosses Claudia T Flynn Nathan R Brady Howard S Fox
author_facet	Mehrdad Alirezaei William B Kiosses Claudia T Flynn Nathan R Brady Howard S Fox
author_sort	Mehrdad Alirezaei
title	Disruption of neuronal autophagy by infected microglia results in neurodegeneration.
title_short	Disruption of neuronal autophagy by infected microglia results in neurodegeneration.
title_full	Disruption of neuronal autophagy by infected microglia results in neurodegeneration.
title_fullStr	Disruption of neuronal autophagy by infected microglia results in neurodegeneration.
title_full_unstemmed	Disruption of neuronal autophagy by infected microglia results in neurodegeneration.
title_sort	disruption of neuronal autophagy by infected microglia results in neurodegeneration.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/56019c7dd51c4684b54b36e56a5dad79
work_keys_str_mv	AT mehrdadalirezaei disruptionofneuronalautophagybyinfectedmicrogliaresultsinneurodegeneration AT williambkiosses disruptionofneuronalautophagybyinfectedmicrogliaresultsinneurodegeneration AT claudiatflynn disruptionofneuronalautophagybyinfectedmicrogliaresultsinneurodegeneration AT nathanrbrady disruptionofneuronalautophagybyinfectedmicrogliaresultsinneurodegeneration AT howardsfox disruptionofneuronalautophagybyinfectedmicrogliaresultsinneurodegeneration
_version_	1718414040470913024

Disruption of neuronal autophagy by infected microglia results in neurodegeneration.

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