amyloid-beta clearance by cellular catabolic process

Definition

Target type: biologicalprocess

The process in which amyloid-beta is removed from extracellular brain regions by cell surface receptor-mediated endocytosis, followed by intracellular degradation. [GOC:aruk, GOC:bc, PMID:18289866]

Amyloid-beta (Aβ) clearance by cellular catabolic processes is a crucial mechanism for maintaining brain health and preventing the accumulation of Aβ, which is a hallmark of Alzheimer's disease. This process involves a complex interplay of various cellular pathways, including:

1. **Endocytosis:** Aβ is internalized into cells through endocytosis, a process where the cell membrane invaginates and engulfs extracellular material. This can occur via clathrin-mediated endocytosis, where Aβ binds to receptors on the cell surface and is internalized within clathrin-coated vesicles, or through other endocytic pathways.

2. **Lysosomal Degradation:** Once inside the cell, Aβ-containing vesicles fuse with lysosomes, which are organelles containing hydrolytic enzymes that break down cellular debris and macromolecules. Within the lysosome, Aβ is degraded into smaller peptides and amino acids, effectively removing it from the cell.

3. **Proteasomal Degradation:** Aβ can also be degraded by the proteasome, a protein complex responsible for degrading misfolded or damaged proteins. This pathway is particularly important for the clearance of intracellular Aβ, which can arise from misfolded Aβ produced within the cell.

4. **Autophagy:** Autophagy is a cellular process that involves the engulfment of cellular components, including protein aggregates, within double-membrane vesicles called autophagosomes. These autophagosomes then fuse with lysosomes, leading to the degradation of the enclosed materials, including Aβ.

The efficiency of Aβ clearance by these pathways can be impaired by various factors, including age, genetic mutations, and environmental factors. This can lead to an accumulation of Aβ in the brain, contributing to the development of Alzheimer's disease.

Furthermore, specific enzymes play critical roles in Aβ clearance, such as:

* **Neprilysin (NEP):** A metallopeptidase that degrades Aβ in the extracellular space.
* **Insulin-degrading enzyme (IDE):** An enzyme involved in the degradation of both insulin and Aβ.
* **Angiotensin-converting enzyme (ACE):** Another metallopeptidase with Aβ-degrading activity.

The intricate interplay of these cellular pathways and enzymes highlights the importance of maintaining efficient Aβ clearance for brain health. Enhancing these pathways through therapeutic interventions could potentially slow or prevent the progression of Alzheimer's disease.'
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Proteins (3)

Compounds (24)