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Even though the implementation of antiretroviral therapy reduced the systemic viral load, the prevalence of HAND remains unchanged and infected patients develop persisting neurological disturbances affecting their quality of life. As a result, HAND have gained importance in basic and clinical researches, warranting the need of developing new adjunctive treatments. Nonetheless, a better understanding of the molecular and cellular mechanisms remains necessary. Several studies consolidated their efforts into elucidating the neurotoxic signaling leading to HAND including the deleterious actions of HIV\u20101 viral proteins and inflammatory mediators. However, the scope of these studies is not sufficient to address all the complexity related to HAND development. Fewer studies focused on an altered neuroprotective capacity of the brain to respond to HIV\u20101 infection. Neurotrophic factors are endogenous polyproteins involved in neuronal survival, synaptic plasticity, and neurogenesis. Any defects in the processing or production of these crucial factors might compose a risk factor rendering the brain more vulnerable to neuronal damages. Due to their essential roles, they have been investigated for their diverse interplays with HIV\u20101 infection. In this review, we present a complete description of the neurotrophic factors involved in HAND. We discuss emerging concepts for their therapeutic applications and summarize the complex mechanisms that down\u2010regulate their production in favor of a neurotoxic environment. For certain factors, we finally address opposing roles that rather lead to increased inflammation.<\/jats:p>","DOI":"10.1002\/glia.23904","type":"journal-article","created":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T06:50:14Z","timestamp":1601189414000},"page":"255-280","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The delicate balance between neurotoxicity and neuroprotection in the context of <scp>HIV<\/scp>\u20101 infection"],"prefix":"10.1002","volume":"69","author":[{"given":"Vincent","family":"S\u00e9n\u00e9cal","sequence":"first","affiliation":[{"name":"Axe des Maladies Infectieuses et Immunitaires Centre de Recherche du CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval, Pavillon CHUL  Qu\u00e9bec Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Barat","sequence":"additional","affiliation":[{"name":"Axe des Maladies Infectieuses et Immunitaires Centre de Recherche du CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval, Pavillon CHUL  Qu\u00e9bec Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6919-7847","authenticated-orcid":false,"given":"Michel J.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Axe des Maladies Infectieuses et Immunitaires Centre de Recherche du CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval, Pavillon CHUL  Qu\u00e9bec Quebec Canada"},{"name":"D\u00e9partement de Microbiologie\u2010infectiologie et immunologie, Facult\u00e9 de M\u00e9decine Universit\u00e9 Laval  Qu\u00e9bec Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-016-0505-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/374450a0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.05.086"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn812"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002906"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6805"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90440-I"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2004.04.001"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0206125"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(02)50083-0"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199710200-00023"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.122450"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0865-12.2012"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-13-05715.2003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2005.tb00032.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20780"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.07.001"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.2.928"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1982.tb01207.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/385640a0"},{"issue":"12","key":"e_1_2_9_22_1","first-page":"816","article-title":"The neuropathology of adult HIV infection","volume":"154","author":"Bell J. 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