Publications by authors named "Alessio-Vittorio Colombo"
Niemann-Pick type C disease (NPC) is a rare inherited neurodegenerative disorder characterized by an accumulation of intracellular cholesterol within late endosomes and lysosomes due to NPC1 or NPC2 dysfunction. In this work, we tested the hypothesis that retromer impairment may be involved in the pathogenesis of NPC and may contribute to increased amyloidogenic processing of APP and enhanced BACE1-mediated proteolysis observed in NPC disease. Using -null cells, primary mouse NPC1-deficient neurons and NPC1-deficient mice (BALB/cNctr-), we show that retromer function is impaired in NPC.
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- Alzheimer's disease (AD) is a leading neurodegenerative disorder often associated with aging, where increased production of amyloid-beta (Aβ) is crucial to its development.
- BACE1, the enzyme responsible for triggering Aβ formation, is influenced by neuronal activity, though the specific mechanisms involved were not fully understood until now.
- This research identifies Casein Kinase 2 as a key player in regulating BACE1 expression through the phosphorylation of eIF4B in neurons, suggesting a link between brain activity and Aβ production, which could lead to new treatment strategies for AD.
Article Synopsis
- - Previous research highlights the gut microbiome's significant influence on the progression of Alzheimer's disease, but the specific mechanisms remained unclear.
- - The study identifies short chain fatty acids (SCFAs) produced by gut bacteria as key factors that increase amyloid beta (Aβ) plaque formation in the brain.
- - Findings show that germ-free mice with Alzheimer’s had fewer Aβ plaques and lower SCFA levels, but adding SCFAs back increased both plaques and altered microglial activity, suggesting SCFAs affect the immune response in the brain.
Article Synopsis
- Microglial dysfunction is a significant aspect of Alzheimer’s disease, yet the specific changes in microglia's protein composition during the disease progression are not well understood.
- This study conducted a detailed analysis of protein changes in microglia from two different mouse models of Alzheimer’s, focusing on how these changes vary at different disease stages.
- Researchers discovered unique protein profiles related to microglial responses to amyloid β deposition, emphasizing that the presence of fibrillar Aβ triggers specific microglial changes, which could serve as potential biomarkers for tracking Alzheimer’s progression or evaluating treatments.
Microglia adopt numerous fates with homeostatic microglia (HM) and a microglial neurodegenerative phenotype (MGnD) representing two opposite ends. A number of variants in genes selectively expressed in microglia are associated with an increased risk for neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Among these genes are progranulin () and the triggering receptor expressed on myeloid cells 2 ().
View Article and Find Full Text PDFBackground: Heterozygous loss-of-function mutations in the progranulin gene (GRN) lead to frontotemporal lobar degeneration (FTLD) while the complete loss of progranulin (PGRN) function results in neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Thus the growth factor-like protein PGRN may play an important role in lysosomal degradation. In line with a potential lysosomal function, PGRN is partially localized and processed in lysosomes.
View Article and Find Full Text PDFMetzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known.
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