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Neuronal autophagy declines substantially with age and is rescued by overexpression of WIPI2.

07:00 EST 3rd December 2019 | BioPortfolio

Summary of "Neuronal autophagy declines substantially with age and is rescued by overexpression of WIPI2."

Macroautophagy/autophagy is implicated in age-dependent neurodegenerative diseases, including amyotrophic lateral sclerosis and Parkinson, Huntington and Alzheimer diseases, suggesting that an age-related decline in neuronal autophagy may contribute to the onset of neurodegeneration. We identified a significant decline in the rate of axonal autophagosome formation in neurons cultured from aged mice, accompanied by a striking increase in the accumulation of autophagic structures with aberrant morphologies. Using live-cell microscopy, we identified the specific step in autophagosome formation that becomes impaired with age, focusing on the role of the phosphoinositide binding protein WIPI2. We determined that the dynamic and local phosphorylation of WIPI2 is a critical regulatory step in autophagosome biogenesis in neurons and that this step is specifically affected by aging. Together, these results provide new insights into the regulation of autophagosome biogenesis in neurons and delineate how autophagosome formation is affected by age. These observations also point to a potential new target for therapeutic intervention.

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This article was published in the following journal.

Name: Autophagy
ISSN: 1554-8635
Pages: 1-2

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Medical and Biotech [MESH] Definitions

Proteins and enzymes that function, often as components of MULTIPROTEIN COMPLEXES, to assemble AUTOPHAGOSOMES and carry out AUTOPHAGY.

An autophagy related protein that is similar to UBIQUITIN-ACTIVATING ENZYME E1. It functions in CYTOPLASM to VACUOLE transport (Cvt) and AUTOPHAGY by activating ATG12 PROTEIN for its conjugation with ATG5 PROTEIN, as well as the conjugation of ATG8 FAMILY PROTEINS with phosphatidylethanolamine for ATG8 association to Cvt vesicles and AUTOPHAGOSOME membranes. It is also required for the nitrogen starvation response in yeast, MITOPHAGY; and autophagic cell death induced by CASPASE 8 inhibition.

Clusters of neuronal cell bodies in invertebrates. Invertebrate ganglia may also contain neuronal processes and non-neuronal supporting cells. Many invertebrate ganglia are favorable subjects for research because they have small numbers of functional neuronal types which can be identified from one animal to another.

A serine/threonine-protein kinase that functions in AUTOPHAGY in response to starvation. It acts on the PHOSPHATIDYLINOSITOL 3-KINASE complex PIK3C3 to regulate AUTOPHAGOSOME formation. It also functions as both a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) and is activated by AMPK, which it also negatively regulates.

An autophagy related protein which functions as a core subunit of PHOSPHATIDYLINOSITOL 3-KINASE MULTIPROTEIN COMPLEXES. It mediates the formation of phosphatidylinositol 3-phosphate and functions in AUTOPHAGY, where it is required for maturation of the AUTOPHAGOSOME. It also functions in ENDOCYTOSIS and CYTOKINESIS as part of a separate complex. Beclin-1 associates with INTRACELLULAR MEMBRANES and interacts with the PROTO-ONCOGENE PROTEINS C-BCL-2 and BCL-X PROTEIN.

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