MAM and C99, key players in the pathogenesis of Alzheimer’s disease
| Autor: | Estela Area-Gomez, Kevin R Velasco, Marta Pera, Delfina Larrea, Rishi R. Agrawal, Irina G Stavrovskaya, Taekyung D Yun, Jorge Montesinos |
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| Rok vydání: | 2020 |
| Předmět: |
Endoplasmic reticulum
Lipid metabolism Biology Mitochondrion medicine.disease Cell biology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Lipid droplet medicine Amyloid precursor protein biology.protein Alzheimer's disease Lipid raft 030217 neurology & neurosurgery |
| Popis: | Inter-organelle communication is a rapidly-expanding field that has transformed our understanding of cell biology and pathology. Organelle-organelle contact sites can generate transient functional domains that act as enzymatic hubs involved in the regulation of cellular metabolism and intracellular signaling. One of these hubs is located in areas of the endoplasmic reticulum (ER) connected to mitochondria, called mitochondria-associated ER membranes (MAM). These MAM are transient lipid rafts intimately involved in cholesterol and phospholipid metabolism, calcium homeostasis, and mitochondrial function and dynamics. In addition, γ-secretase-mediated proteolysis of the amyloid precursor protein 99-aa C-terminal fragment (C99) to form amyloid β also occurs at the MAM. Our most recent data indicates that in Alzheimer's disease, increases in uncleaved C99 levels at the MAM provoke the upregulation of MAM-resident functions, resulting in the loss of lipid homeostasis, and mitochondrial dysfunction. Here, we discuss the relevance of these findings in the field, and the contribution of C99 and MAM dysfunction to Alzheimer's disease neuropathology. |
| Databáze: | OpenAIRE |
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