Microglial and Neuronal Autophagy

[Mar. 19, 2024] Previous Science Note

Autophagy is a cellular process that degrades and recycles damaged organelles, misfolded proteins, and other cellular debris, and is critical for maintaining cellular homeostasis. Dysregulated autophagy is often observed in the context of neurodegeneration, where either excessive or insufficient autophagic activity can contribute to the accumulation of toxic proteins and organelle dysfunction that are hallmarks of neurodegenerative diseases. Enhancing autophagy has been shown to alleviate symptoms and pathology in models of diseases such as Alzheimer's, Parkinson's, and Huntington's, suggesting a protective role against neurodegeneration. Conversely, excessive autophagy can lead to cell death, suggesting that a delicate balance is required for neuronal health and highlighting the complexity of targeting autophagy as a therapeutic strategy for neurodegenerative diseases.

Autophagy enables microglia to engage amyloid plaques and prevents microglial senescence
Click here for the original article: Insup Choi, et. al., Nature Cell Biology, 2023.

Point of Interest
- Inhibiting microglial autophagy leads to the disengagement of microglia from amyloid plaques, exacerbating neuropathology in mice with Alzheimer's Disease (AD).

- An autophagy deficiency fosters the development of senescent microglia.

- Pharmacological removal of autophagy-deficient senescent microglia can alleviate neuropathology in mice with AD.

Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration
Click here for the original article: Beatrice Paola Festa, et. al., Neuron, 2023.

Point of Interest
- Activated microglia mediate non-cell-autonomous inhibition of neuronal autophagy.

- CCL-5, CCL-4, and CCL-3 derived from microglia activate the neuronal CCR5 receptor, leading to the inhibition of neuronal autophagy.

- Levels of CCR5, CCL-3, CCL-4, and CCL-5 are elevated in the brains of mice with Huntington’s disease and tauopathy.

- Inhibiting CCR5, either pharmacologically or genetically, ameliorates neurodegeneration in mice.

Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer’s disease
Click here for the original article: Lauren H. Fairley, et. al., PNAS, 2022.

Point of Interest
- The translocator protein (TSPO) is pivotal for respiratory metabolism and energy supply in microglia.

- Hexokinase-2 (HK) affects glycolytic metabolism and phagocytosis through its interaction with mitochondria.

- Mitochondrial HK influences glycolysis and inflammation, and its displacement improves phagocytosis in TSPO-deficient microglia.

- Alzheimer’s beta-amyloid drastically stimulated mitochondrial HK recruitment in cultured microglia, which may contribute to microglial dysfunction in Alzheimer’s disease.

Related Techniques

Detection (Reagent) Samples Reference
Autophagosome/ Autolysosome
(Autophagic Flux Assay Kit)
Immortalized Fischer rat Schwann cells International Journal of Molecular Sciences
Autolysosome
(DALGreen)
Cortical neurons Neurobiology of Disease
PC12 cells (a mixture of neuroblastic cells and eosinophilic cells) Hindawi
Autophagosome
(DAPGreen or DAPRed)
Neurons from mouse embryonic stem cells Life Science Alliance
Hippocampal neurons PNAS
N2a cells (Mouse Albino neuroblastoma) International Journal of Molecular Sciences
Mitophagy
(Mtphagy Dye)
Neural progenitor cell (NPC) International Journal of Molecular Sciences
Primary cortical neuronal (CxN) cells Cells
Brain slices (mice) The FEBS Journal

Link to each product (red at left figure)

Autophagy Detection
 Autophagic Flux Assay Kit - First-choice product
 DAPRed - Autophagosome detection
 DAPGreen - Autophagosome detection
 DALGreen - Autolysosome detection

Mitophagy Detection
 Mitophagy Detection Kit and Mtphagy Dye

Mitochondrial Membrane Potential Detection
 JC-1 / MT-1

Lysosomal Analysis
 Lysosomal Acidic pH Detection Kit
 Green/RedGreen/Deep Red

Endocytosis Detection
 ECGreen-Endocytosis Detection
 AcidSensor Labeling Kit

Exosome
 Exosome Isolation Kit
 Exosome Membrane Labeling Kit
 Green / Red / Deep Red

Product Classification

Product Classification