Related Experiment Video

Updated: Jun 19, 2026

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice
10:13

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice

Published on: August 12, 2014

Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P2

Cole J Ferguson1, Guy M Lenk, Miriam H Meisler

  • 1Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA.

Human Molecular Genetics
|October 2, 2009
PubMed

Insights

Mutations in PI(3,5)P(2) regulation cause brain degeneration and are linked to neurodegenerative diseases. Impaired autophagy in neurons and astrocytes suggests a role for this lipid in inclusion body disease.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Mutations in phosphoinositide metabolism, specifically the conversion of PI3P to PI(3,5)P(2), lead to spongiform brain degeneration in mice.
  • These mutations are implicated in human neurological disorders, including Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis (ALS).

Purpose of the Study:

  • To investigate the cellular mechanisms underlying neurodegeneration caused by mutations affecting the PI(3,5)P(2) regulatory complex.
  • To determine the role of PI(3,5)P(2) in autophagy within the mammalian central nervous system (CNS).

Main Methods:

  • Analysis of protein accumulation (LC3-II, p62, LAMP-2) in neurons and astrocytes of mice with mutations in Fig4 and Vac14.
  • Histopathological examination of mutant mouse brains to identify inclusion bodies and assess cellular degeneration.
  • Assessing co-localization of p62 and LAMP-2 to evaluate autolysosome formation or recycling.

Main Results:

  • Accumulation of LC3-II, p62, and LAMP-2 proteins was observed in neurons and astrocytes of mutant mice.
  • Cytoplasmic inclusion bodies containing p62 and ubiquitinated proteins were found in degenerating brain regions.
  • Impaired autolysosome formation or recycling was indicated by the co-localization of p62 and LAMP-2 in affected cells.

Conclusions:

  • PI(3,5)P(2) plays a crucial role in autophagy within the mammalian CNS.
  • Mutations affecting PI(3,5)P(2) can lead to the development of inclusion body disease through impaired autophagic processes.

More Related Videos

A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes06:43

A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes

Published on: February 5, 2018

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy09:29

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

Related Concept Videos

Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...