What is the amyloidogenic pathway?

What is the amyloidogenic pathway?

The amyloidogenic pathway is the process of Aβ biogenesis: APP is firstly cleaved by β-secretase, producing soluble β-APP fragments (sAPPβ) and C-terminal β fragment (CTFβ, C99), and C99 is further cleaved by γ-secretase, generating APP intracellular domain (AICD) and Aβ.

What are amyloidogenic proteins?

Amyloidogenic proteins are typically soluble monomeric precursors, which undergo remarkable conformation changes associated with the polymerization into 8- to 10-nm wide fibrils, which culminate in the formation of amyloid aggregates.

How does gamma secretase work?

With more than 90 known substrates, the γ-secretase complex is considered “the proteasome of the membrane”, with central roles in biology and medicine. The protease carries out hydrolysis within the lipid bilayer to cleave the transmembrane domain of the substrate multiple times before releasing secreted products.

What is the role of APP?

Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator of synapse formation, neural plasticity, antimicrobial activity, and iron export.

What causes the amyloidogenic pathway?

Oxidative Stress Caused by Ozone Exposure Induces β- amyloid 1-42 overproduction and Mitochondrial Accumulation by Activating the Amyloidogenic pathway.

What are gamma secretase inhibitors?

γ-Secretase inhibitors (GSI) are a class of small-molecule inhibitors that, as the name implies, prevent the cleavage of γ-secretase substrates. A number of GSIs were developed after γ-secretase was identified as an enzyme responsible for the accumulation of β-amyloid in Alzheimer’s disease (11, 12).

Does everyone have a copy of APP gene?

Because you inherit one APOE gene from your mother and another from your father, you have two copies of the APOE gene. If you have two APOE e4 genes, your risk is even higher, approximately eight- to twelvefold. But not everyone who has one or even two APOE e4 genes develops Alzheimer’s disease.