HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders

Yasmin Zeinolabediny, Francesca Caccuri, Laura Colombo, Federica Morelli, Margherita Romeo, Alessandro Rossi, Silvia Schiarea, Carlotta Ciaramelli, Cristina Airoldi, Ria Weston, Liu Donghui, Jerzy Krupinski, Rubén Corpas, Elisa García-Lara, Sara Sarroca, Coral Sanfeliu, Mark Slevin, Arnaldo Caruso, Mario Salmona, Luisa Diomede

Research output: Contribution to journalArticle

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Abstract

Human immunodeficiency virus type-1 (HIV-1)-Associated neurocognitive disorder (HAND) remains an important neurological manifestation that adversely affects a patient's quality of life. HIV-1 matrix protein p17 (p17) has been detected in autoptic brain tissue of HAND individuals who presented early with severe AIDS encephalopathy. We hypothesised that the ability of p17 to misfold may result in the generation of toxic assemblies in the brain and may be relevant for HAND pathogenesis. A multidisciplinary integrated approach has been applied to determine the ability of p17 to form soluble amyloidogenic assemblies in vitro. To provide new information into the potential pathogenic role of soluble p17 species in HAND, their toxicological capability was evaluated in vivo. In C. elegans, capable of recognising toxic assemblies of amyloidogenic proteins, p17 induces a specific toxic effect which can be counteracted by tetracyclines, drugs able to hinder the formation of large oligomers and consequently amyloid fibrils. The intrahippocampal injection of p17 in mice reduces their cognitive function and induces behavioral deficiencies. These findings offer a new way of thinking about the possible cause of neurodegeneration in HIV-1-seropositive patients, which engages the ability of p17 to form soluble toxic assemblies.

Original languageEnglish
Article number10313
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Poisons
HIV-1
Aptitude
AIDS Dementia Complex
Amyloidogenic Proteins
Tetracyclines
Brain
Neurologic Manifestations
Amyloid
Toxicology
Cognition
Quality of Life
Neurocognitive Disorders
p17 protein, Human Immunodeficiency Virus Type 1
Injections
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

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HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders. / Zeinolabediny, Yasmin; Caccuri, Francesca; Colombo, Laura; Morelli, Federica; Romeo, Margherita; Rossi, Alessandro; Schiarea, Silvia; Ciaramelli, Carlotta; Airoldi, Cristina; Weston, Ria; Donghui, Liu; Krupinski, Jerzy; Corpas, Rubén; García-Lara, Elisa; Sarroca, Sara; Sanfeliu, Coral; Slevin, Mark; Caruso, Arnaldo; Salmona, Mario; Diomede, Luisa.

In: Scientific Reports, Vol. 7, No. 1, 10313, 01.12.2017.

Research output: Contribution to journalArticle

Zeinolabediny, Y, Caccuri, F, Colombo, L, Morelli, F, Romeo, M, Rossi, A, Schiarea, S, Ciaramelli, C, Airoldi, C, Weston, R, Donghui, L, Krupinski, J, Corpas, R, García-Lara, E, Sarroca, S, Sanfeliu, C, Slevin, M, Caruso, A, Salmona, M & Diomede, L 2017, 'HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders', Scientific Reports, vol. 7, no. 1, 10313. https://doi.org/10.1038/s41598-017-10875-0
Zeinolabediny, Yasmin ; Caccuri, Francesca ; Colombo, Laura ; Morelli, Federica ; Romeo, Margherita ; Rossi, Alessandro ; Schiarea, Silvia ; Ciaramelli, Carlotta ; Airoldi, Cristina ; Weston, Ria ; Donghui, Liu ; Krupinski, Jerzy ; Corpas, Rubén ; García-Lara, Elisa ; Sarroca, Sara ; Sanfeliu, Coral ; Slevin, Mark ; Caruso, Arnaldo ; Salmona, Mario ; Diomede, Luisa. / HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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