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.


Journal Details

This article was published in the following journal.

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


DeepDyve research library

PubMed Articles [6331 Associated PubMed Articles listed on BioPortfolio]

Icariside II, a phosphodiesterase 5 inhibitor, attenuates cerebral ischemia/reperfusion injury by inhibiting GSK-3β-mediated activation of autophagy.

Cerebral ischemia/reperfusion (I/R) is always exacerbated neuronal damage when timely restoring cerebral blood flow after ischemia stroke. Cerebral I/R results in excessive autophagy and neuronal demi...

Autophagy in Neurons.

Autophagy is the major cellular pathway to degrade dysfunctional organelles and protein aggregates. Autophagy is particularly important in neurons, which are terminally differentiated cells that must ...

Apolipoprotein A-I improves hepatic autophagy through the AMPK pathway.

Dysfunction in lipid metabolism may result in a decrease in hepatic autophagy, which contributes to the pathogenesis of non-alcoholic steatohepatitis. ATP-binding cassette transporter A1 transports fr...

Over-expression of lncRNA TCTN2 protects neurons from apoptosis by enhancing cell autophagy in spinal cord injury.

Neuronal apoptosis is the main pathological feature of spinal cord injury (SCI), while autophagy contributes to ameliorating neuronal damage via inhibition of apoptosis. Here, we investigated the role...

The signaling axis of Rac1-TFEB regulates autophagy and tumorigenesis.

Macroautophagy (hereafter referred to as autophagy) plays essential roles in cellular and organismal homeostasis. Transcription factor EB (TFEB) is a master regulator of autophagy and lysosome biogene...

Clinical Trials [926 Associated Clinical Trials listed on BioPortfolio]

Study of Autophagy and the Effects of GALIG Gene Products in HIV-1 Infected Patients Who Are Under Antiretroviral Therapy Since Primary-infection, Chronic Phase, or Never Treated.

Little is known about autophagy during HIV infection. Recently, two different teams reported important dysfunctions of autophagy in HIV-infected patients despite sustained suppressive anti...

Autophagy and Pathological Aging

Autophagy is recognized as a central mechanism for the regulation of aging. . Osteoporosis (OA) and Alzheimer's disease (AD) are two forms of pathological aging, sometimes entangled, inclu...

Correlation Between Autophagy-related Proteins and Inflammatory Markers in Hemodialysis Patients

One recent study demonstrated impaired autophagy in patients receiving hemodialysis (HD). To clarify whether this alteration is related to the inflammatory state in HD patients, we focused...

Autophagy and Venous Endothelial Function

The molecular mechanisms involved in venous endothelial dysfunction are largely unknowns. Autophagy is an intracellular mechanism devoted to the removal of damaged cytoplasmic elements. Pr...

Expression of LC3-I, LC3-II & Beclin 1 in Vitiligo

The exact mechanism of impairment of autophagy in vitiligo has not yet been determined.

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.

Quick Search

DeepDyve research library

Relevant Topics

Parkinson's Disease
Parkinson's is a progressive neurological condition, affecting one person in every 500, 95% of which are over 40. It is caused by degeneration of more than 70% of the substantia nigra, which depletes the dopamine (the neurotransmitter involved in pro...

Huntington's Disease
Huntington's disease is a hereditary disease caused by a defect in a single gene on Chromosome 4 that is inherited in an autosomal dominant fashion. The defect causes a part of DNA, called a CAG repeat, to occur many more times than it is supposed to...

Searches Linking to this Article