Dataset Information

HIV-1 gp120 impairs spatial memory through CREB

ABSTRACT: HIV-associated neurocognitive disorders (HAND) remain an unsolved problem that persists despite using antiretroviral therapy. We have obtained data showing that HIV-gp120 protein contributes to neurodegeneration through metabolic reprogramming. This led to decreased ATP levels, lower mitochondrial DNA copy numbers, and loss of mitochondria cristae, all-important for mitochondrial biogenesis. gp120 protein also disrupted mitochondrial movement and synaptic plasticity. Searching for the mechanisms involved, we found that gp120 alters the cyclic AMP response element-binding protein (CREB) phosphorylation on serine residue 133 necessary for its function as a transcription factor. Since CREB regulates the promoters of PGC1 and BDNF genes, we found that CREB dephosphorylation causes PGC1 and BDNF loss of functions. Our data was validated in vitro and in vivo. The negative effect of gp120 was alleviated in cells and animals in the presence of rolipram that inhibits the phosphodiesterase protein 4 (PDE4) and restores CREB phosphorylation. We concluded that HIV-gp120 protein contributes to HAND via inhibition of CREB protein function.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Neuron Associated Cell

DISEASE(S): Acquired Immunodeficiency Syndrome

SUBMITTER: Carmen Merali

LAB HEAD: Salim Merali, Ph.D.

PROVIDER: PXD031891 | Pride | 2022-06-09

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	ELITE_Sawaya10_gp120C_treated_SCX1.raw	Raw
	ELITE_Sawaya10_gp120C_treated_SCX2.raw	Raw
	ELITE_Sawaya10_gp120C_treated_SCX3.raw	Raw
	ELITE_Sawaya10_gp120C_treated_SCX4.raw	Raw
	ELITE_Sawaya10_gp120C_treated_SCX5.raw	Raw

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Publications

HIV-1 gp120 Impairs Spatial Memory Through Cyclic AMP Response Element-Binding Protein.

Shrestha Jenny J Santerre Maryline M Allen Charles N S CNS Arjona Sterling P SP Merali Carmen C Mukerjee Ruma R Chitrala Kumaraswamy Naidu KN Park Jin J Bagashev Asen A Bui Viet V Eugenin Eliseo A EA Merali Salim S Kaul Marcus M Chin Jeannie J Sawaya Bassel E BE

Frontiers in aging neuroscience 20220509

HIV-associated neurocognitive disorders (HAND) remain an unsolved problem that persists despite using antiretroviral therapy. We have obtained data showing that HIV-gp120 protein contributes to neurodegeneration through metabolic reprogramming. This led to decreased ATP levels, lower mitochondrial DNA copy numbers, and loss of mitochondria <i>cristae</i>, all-important for mitochondrial biogenesis. gp120 protein also disrupted mitochondrial movement and synaptic plasticity. Searching for the mec ...[more]

PMID: 35615594

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