Topic: synaptic loss

Recent data propose that Alzheimer’s disease (AD) should be considered as a systemic disease with a strong immune component. However, direct targeting of the immune system contribution to AD has been so far minimally explored. Here, by using a systems biology approach based on network integration of text mining and genomic data, we identified glucose‐6‐phosphate dehydrogenase (G6PD) as a target that may modulate neutrophil function and, in turn, down-regulate the immune system related damage in AD. Pharmacological and siRNA modulation, performed in differentiated HL-60 cells and primary neutro

Cellular hallmarks of neurodegenerative diseases include loss of synapses, neuronal death, inflammation, energy homeostasis defects, oxidative stress, mitochondrial dysfunction, and aberrant proteostasis. AMP-activated kinase (AMPK) maintains energy homeostasis by responding to fluctuating ATP levels, with diverse targets ranging from changing the transcriptional program, promoting glucose uptake, inhibiting protein synthesis, inducing mitochondrial fission, mitophagy and autophagy. Evidence indicates that AMPK is hyperactivated in Alzheimer’s disease (AD), and amyloid-β (Aβ) can activate AMPK

Alzheimer's disease (AD) is characterized by an early hippocampus hyperactivity triggered by Aβ oligomers (Aβo) in humans and AD mouse models, followed by hypoactivity and synaptic loss occurring before cognitive decline. GWAS identified PTK2B gene encoding for Pyk2, a tyrosine kinase involved in synaptic plasticity, as a new AD risk factor. Several studies have validated Pyk2 involvement in AD pathophysiology, but its exact role is still debated due to conflicting results. The objective of this project is to decipher the role of Pyk2 in synaptic dysfunctions observed in this disease. We first

Neurodegenerative diseases like Alzheimer’s disease and Progressive Supranuclear Palsy (PSP) exhibit synaptic loss. In these conditions, synaptic loss precedes neuronal degeneration, and the degree of synaptic loss correlates closely with the severity of clinical symptoms. Both Aβ, which accumulates in amyloid plaques in AD, and tau protein which accumulates intracellularly in tauopathies, accumulate within synaptic terminals. In model systems, the accumulation of Aβ and tau in synapses has been linked to synaptic dysfunction, synaptic loss, and the spread of pathology trans-synaptically. Howe