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Protecting the Synapse: Evidence for a Rational Strategy to Treat HIV-1 Associated Neurologic Disease

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Abstract

Loss of synaptic integrity and function appears to underlie neurologic deficits in patients with HIV-1-associated dementia (HAD) and other chronic neurodegenerative diseases. Because synaptic injury often long precedes neuronal death and surviving neurons possess a remarkable capacity for synaptic repair and functional recovery, we hypothesize that therapeutic intervention to protect synapses has great potential to improve neurologic function in HAD and other diseases. We discuss findings from both HAD and Alzheimer's disease to demonstrate that the disruption of synaptic structure and function that can occur during excitotoxic injury and neuroinflammation represents a likely substrate for neurologic deficits. Based on available evidence, we provide a rationale for future studies aimed at identifying molecular targets for synaptic protection in neurodegenerative disease. Whereas patients with HAD beginning antiretroviral therapy have shown reversal of neurologic symptoms that is unique for patients with chronic neurodegenerative conditions, we propose that the potential for such reversal is not unique.

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Acknowledgements

This work was supported by grants from the US National Institutes of Health (MH64570, MH56838, MH71176, and NS31492 to M.J.B., S.M.L., and H.A.G.; AI49815 and GM07356 to M.J.B.). M.J.B. is in the Medical Scientist Training Program.

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Bellizzi, M.J., Lu, SM. & Gelbard, H.A. Protecting the Synapse: Evidence for a Rational Strategy to Treat HIV-1 Associated Neurologic Disease. Jrnl NeuroImmune Pharm 1, 20–31 (2006). https://doi.org/10.1007/s11481-005-9006-y

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