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Inadequate secretion of intrinsic factor, resulting from lesions that destroy the gastric mucosa (ingestion of corrosives, extensive neoplasia), and a number of conditions associated with a variable degree of gastric atrophy (such as multiple sclerosis, HIV infection, AIDS, certain endocrine disorders, iron deficiency, and subtotal gastrectomy)

The early role of UPR is to reduce translation to lessen the need for new protein folding, degrade unfolded proteins to minimize damage, and increase the expression of chaperone proteins to assist protein folding