Inhibition of zDHHC7-Driven Protein S-Palmitoylation Prevents Cognitive Deficits in Alzheimer's Disease

Summary: A groundbreaking study published in PNAS reveals how zDHHC7-driven protein S-palmitoylation contributes to cognitive deficits in Alzheimer's disease (AD). Key findings include:

• Mechanism of Impairment: Elevated zDHHC7 expression in the hippocampus increases S-palmitoylation of proteins like BACE1, disrupting synaptic plasticity and promoting amyloid-beta (Aβ) deposition.
• Impact on Memory: Aberrant S-palmitoylation levels correlate with cognitive decline in AD mouse models and human hippocampal samples, linking these molecular changes directly to memory impairment.
• Therapeutic Potential: The palmitoylation inhibitor 2-bromopalmitate (2-BP) and hippocampal zDHHC7 silencing reversed synaptic deficits, reduced Aβ levels, and improved cognition in AD mouse models.
• Broader Implications: This research underscores protein S-palmitoylation as a key target for developing AD treatments, offering hope for tackling this neurodegenerative disease.

References: Natale, F., Spinelli, M., Rinaudo, M., et al. (2024). Inhibition of zDHHC7-driven protein S-palmitoylation prevents cognitive deficits in an experimental model of Alzheimer’s disease. PNAS, 121(49), e2402604121. DOI: 10.1073/pnas.2402604121.

Hashtags: #AlzheimersDisease #CognitiveDecline #SynapticPlasticity #ProteinPalmitoylation #Neurodegeneration #TherapeuticTargets #Neuroscience