Related Experiment Video
Updated: Apr 23, 2026
07:18
Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia
Published on: November 9, 2018
9.8K
PICALM modulates autophagy activity and tau accumulation
Kevin Moreau1, Angeleen Fleming2, Sara Imarisio3
1Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
Nature Communications
|September 23, 2014
Summary
Phosphatidylinositol binding clathrin assembly protein (CALM) influences Alzheimer's disease (AD) pathology by modulating autophagy and tau protein clearance. CALM
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Genome-wide association studies link Alzheimer's disease (AD) risk loci to endocytic trafficking proteins like PICALM/CALM.
- The precise mechanisms by which these genetic factors contribute to AD pathogenesis remain largely unknown.
Purpose of the Study:
- To investigate the role of CALM in modulating autophagy and tau protein clearance in Alzheimer's disease.
- To elucidate how CALM influences cellular processes relevant to AD pathology.
Main Methods:
- In vitro and in vivo experiments to assess CALM's effect on autophagy.
- Utilized zebrafish transgenic models to study CALM's impact on tau-mediated toxicity.
- Examined CALM's regulation of SNARE proteins involved in endocytosis and autophagy.
Main Results:
- CALM was found to modulate autophagy and alter the clearance of tau protein, a key player in AD.
- Altered CALM expression in zebrafish models exacerbated tau-related neurotoxicity.
- CALM regulates the endocytosis of SNAREs, impacting autophagosome formation and degradation.
Conclusions:
- The Alzheimer's disease genetic risk factor CALM plays a significant role in modulating autophagy.
- CALM's influence on tau turnover and autophagy presents a potential therapeutic target for Alzheimer's disease.
Related Concept Videos
01:18Autophagic Cell Death
3.3K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.3K
01:16Calmodulin-dependent Signaling
4.9K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
4.9K
01:27Autophagy
5.0K
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,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.0K
01:22PI3K/mTOR/AKT Signaling Pathway
5.1K
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...
5.1K
01:25cAMP-dependent Protein Kinase Pathways
7.2K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
7.2K
01:22Cellular Injury V: Apoptosis and Autophagy
57
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
57