amyloid-beta clearance

Definition

Target type: biologicalprocess

The process in which amyloid-beta is removed from extracellular brain regions by mechanisms involving cell surface receptors. [GOC:aruk, GOC:bc, GOC:BHF, PMID:18289866, PMID:19098903, PMID:26005850]

Amyloid-beta (Aβ) clearance is a complex process involving multiple cellular and molecular mechanisms that remove Aβ from the brain. Aβ is a peptide fragment produced from the amyloid precursor protein (APP) and is thought to be a major contributor to the development of Alzheimer’s disease. There are multiple pathways involved in the clearance of Aβ, including:

1. **Degradation:**
* **Enzymatic degradation:** Enzymes such as neprilysin, insulin-degrading enzyme (IDE), and endothelin-converting enzyme (ECE) can break down Aβ into smaller, less toxic fragments. These enzymes are found in the brain and other tissues, and their activity is regulated by a variety of factors.
* **Proteasomal degradation:** The proteasome is a large protein complex responsible for degrading misfolded and damaged proteins, including Aβ.

2. **Cellular uptake and efflux:**
* **Microglial phagocytosis:** Microglia are the primary immune cells of the brain and are responsible for engulfing and removing Aβ.
* **Astrocyte uptake:** Astrocytes are star-shaped glial cells that play a role in supporting neurons. They can also take up Aβ and transport it to other cells or degrade it themselves.
* **Blood-brain barrier (BBB) efflux:** The BBB is a protective barrier that prevents harmful substances from entering the brain. Special proteins, such as the low-density lipoprotein receptor-related protein 1 (LRP1), can transport Aβ across the BBB and out of the brain.

3. **Extracellular clearance:**
* **Drainage through the lymphatic system:** The lymphatic system is a network of vessels that collects fluid from the body and transports it to the bloodstream. Research suggests that Aβ may be cleared from the brain through the lymphatic system.
* **Glymphatic system:** The glymphatic system is a recently discovered network of fluid channels in the brain that helps to remove waste products, including Aβ.

4. **Other pathways:**
* **Aggregation and deposition:** Aβ can aggregate into toxic oligomers and plaques that contribute to neurodegeneration. While this is not directly clearance, it can influence the process.

The efficiency of Aβ clearance is crucial for maintaining brain health. Dysregulation of any of the pathways involved in Aβ clearance can lead to Aβ accumulation in the brain, which can contribute to the development of Alzheimer’s disease. Research is ongoing to better understand the intricate mechanisms of Aβ clearance and to develop new therapies that can target these pathways and promote healthy brain aging.'
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Proteins (8)

Compounds (333)