Final answer:
Amyloid peptides are generated from APP and are found outside of the cell, forming amyloid plaques characteristic of Alzheimer's disease. Peripheral membrane proteins synthesized within the ER end up on the outside of the plasma membrane. Protein misfolding can lead to toxic accumulations, as seen in 'proteopathy' diseases including Alzheimer's and Creutzfeld-Jacob disease.
Step-by-step explanation:
Amyloid peptides are generated from the cleavage of the amyloid precursor protein (APP) and they are primarily found outside of the cell, forming extracellular amyloid plaques. These plaques are a hallmark in the brains of patients with Alzheimer's disease. The process of amyloid beta (Aβ) peptide production involves enzymatic cleavage that leads to these peptides, which under normal circumstances are further digested to prevent build-up. However, an unregulated formation or insufficient clearance of Aβ leads to the characteristic plaques associated with Alzheimer's. These plaques consist of misfolded proteins that transition from soluble α-helices into β-pleated sheets, which are prone to aggregation.
If a peripheral membrane protein is synthesized within the lumen of the endoplasmic reticulum (ER), it will end up on the outside of the plasma membrane after the ER-Golgi network processes it and secretes it via exocytosis. This is due to the topological continuity between the lumen of the ER and the extracellular space. Furthermore, the folding of proteins into their functional three-dimensional shapes is crucial for their proper function. Misfolding can lead to these proteins becoming nonfunctional or, in some cases, toxic when they accumulate, as seen with amyloid plaques in neurological diseases like Alzheimer's and Creutzfeld-Jacob disease. This is termed 'proteopathy', a disease category that also includes conditions like cystic fibrosis and type 2 diabetes, where protein accumulation can be harmful.