Question

What proteins are involved in the formation of the destructive plaques found in Alzheimer's disease?

Short answer

The main protein is Amyloid beta (Aβ), derived from Amyloid precursor protein (APP) through the action of beta-secretase and gamma-secretase enzymes.

Step-by-step solution

Identify the main protein involved

The primary protein associated with the formation of plaques in Alzheimer's disease is Amyloid beta (Aβ). These proteins aggregate to form plaques.

Understand the role of Amyloid precursor protein (APP)

The Amyloid precursor protein (APP) is a larger protein that, when cleaved by certain enzymes, produces Amyloid beta peptides. These peptides can accumulate and form plaques.

Role of enzymes in plaque formation

Enzymes like beta-secretase and gamma-secretase cleave APP to produce the Aβ peptides. Misprocessing of APP by these enzymes often leads to the formation of the destructive plaques characteristic of Alzheimer's disease.

Key concepts

Amyloid Beta

Amyloid beta (Aβ) is a small protein that plays a crucial role in the formation of plaques seen in Alzheimer's disease. Normally, Aβ peptides are produced in small amounts and are cleared away by the brain.

However, under certain conditions, these peptides can aggregate and form larger structures. This accumulation results in the sticky and toxic plaques that disrupt brain function.

Amyloid beta is notable because it is the main component of these plaques. Understanding the formation and behavior of Aβ is vital for developing treatments for Alzheimer's disease. Misfolding and accumulation of these proteins are central to the pathology of the disease.

Amyloid Precursor Protein (APP)

Amyloid precursor protein (APP) is a larger protein from which Amyloid beta (Aβ) is derived.
APP spans the membrane of neurons in the brain and is involved in normal cell functions, including cell growth and repair.

To produce Aβ, APP undergoes a process called proteolytic cleavage. This involves slicing APP into smaller pieces. The key players in this process are beta-secretase and gamma-secretase enzymes.

When APP is cleaved correctly, it produces Aβ peptides that can be managed by the brain. However, when this process goes awry, the resulting Aβ peptides can accumulate and form plaques. These plaques are one of the hallmarks of Alzheimer's disease and are linked to the malfunction and death of neurons.

Beta-Secretase and Gamma-Secretase

Beta-secretase and gamma-secretase are essential enzymes in the formation of Amyloid beta (Aβ) peptides from the Amyloid precursor protein (APP).

Beta-secretase initiates the cleavage by cutting the APP at a specific site, producing a fragment. Gamma-secretase then takes over, making another cut within the membrane-spanning region of the APP.

The combined action of these enzymes results in the release of Aβ peptides into the extracellular space.

If these peptides are not cleared efficiently, they start to aggregate and form plaques, contributing to brain degeneration in Alzheimer's disease. It is the disrupted activity or misprocessing by these enzymes that often leads to pathological plaque formation. Understanding and regulating these enzymes is a critical area of research in Alzheimer's therapy.