ALPHA-0702 and ALPHA-0802 (GEMs)

Progranulin is comprised of 7½ Granulin Epithelin Motifs (GEMs). GEMs are important in regulating cell growth, survival, repair, and inflammation

Individual granulin domain peptides are approximately 60 amino acids in length (~7kDa). GEMs are metabolically stable and resistant to proteolysis (long half-life)

Evidence suggests that not all GEMs are equally potent at promoting cell survival signaling or reducing proteinopathy, and may compete (e.g., binding to effectors) with active GEMs and effectively decrease their potency

Specific GEM combinations have been shown to be more effective than full length progranulin in promoting Cathepsin D maturation

Image source: Saint Louis University Chart: PROTEIN-CODING REGION OF HUMAN GRN GENE-chromosome https://nguyen-lab.com/slu/research/

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