Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

Area of Science:

• Neuroscience
• Biochemistry
• Infectious Diseases

Background:

• Individuals with HIV-1 infection have a high prevalence of HIV-1-associated neurocognitive disorders (HAND).
• No effective treatments are currently available for HAND, which is linked to neuronal injury caused by viral and cellular factors, including HIV-1 Tat.
• Mitochondrial dysfunction and oxidative stress are implicated in HAND pathogenesis.

Purpose of the Study:

• To investigate the protective effects of creatine against HIV-1 Tat-induced neuronal injury.
• To determine if creatine prevents mitochondrial bioenergetic crisis and redox catastrophe in the context of HIV-1 Tat exposure.

Main Methods:

• Neuronal cell cultures were treated with HIV-1 Tat(1-72) and creatine.
• Assessed neuron cell death, synaptic area loss, ATP levels, and mitochondrial function (hypopolarization and permeability transition pore opening).
• Measured cellular creatine and phosphocreatine levels.

Main Results:

• Creatine significantly blocked HIV-1 Tat(1-72)-induced increases in neuron cell death and synaptic area loss.
• Creatine prevented decreases in ATP levels caused by HIV-1 Tat.
• Creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and mitochondrial permeability transition pore opening.

Conclusions:

• Creatine demonstrates neuroprotective effects against HIV-1 Tat-induced neuronal injury.
• Creatine mitigates mitochondrial dysfunction and bioenergetic crisis associated with HIV-1 Tat.
• Creatine shows potential as an adjunctive therapy for managing HIV-1-associated neurocognitive disorders.