Zhongshuai Wang1, Yan Yan1, Baoxi Wang2. 1. Department of Dermatology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 2. Department of Dermatology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, wangbx@vip.126.com.
Abstract
BACKGROUND: Acne inversa/hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease of the skin that can significantly affect patients' quality of life. The etiology and pathogenesis of HS are unclear and gene mutations might play a role. SUMMARY: The primary focus of the review is on aggregating the gene mutations reported, summarizing the structure of γ-secretase and analyzing and speculating about the mechanism and the underlying relations between gene mutation and functional changes of protein. The systematic literature review was done by searching the PubMed, Embase, and Web of Science databases. γ-Secretase is an intramembrane protease complex responsible for the intramembranous cleavage of more than 30 type-1 transmembrane proteins including amyloid precursor protein and Notch receptors. The protein complex consists of four hydrophobic proteins: presenilin, presenilin enhancer-2 (PSENEN), nicastrin, and anterior pharynx defective 1 (APH1). To date, 57 mutations of γ-secretase genes have been reported in 70 patients or families worldwide, including 39 in NCSTN, 14 in PSENEN, and 4 in PSEN1, of which 17 are frameshifts, 15 result in nonsense mutations, 13 in missense mutations, and 12 are splice site mutations. Given the structure of γ-secretase and analysis of related mutation loci of NCSTN, PSENEN, and PSEN1, mutations in γ-secretase genes could affect activation of presenilin, prevent substrate binding, and hinder intramembrane cleavage of select proteins. The Author(s). Published by S. Karger AG, Basel.
BACKGROUND: Acne inversa/hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease of the skin that can significantly affect patients' quality of life. The etiology and pathogenesis of HS are unclear and gene mutations might play a role. SUMMARY: The primary focus of the review is on aggregating the gene mutations reported, summarizing the structure of γ-secretase and analyzing and speculating about the mechanism and the underlying relations between gene mutation and functional changes of protein. The systematic literature review was done by searching the PubMed, Embase, and Web of Science databases. γ-Secretase is an intramembrane protease complex responsible for the intramembranous cleavage of more than 30 type-1 transmembrane proteins including amyloid precursor protein and Notch receptors. The protein complex consists of four hydrophobic proteins: presenilin, presenilin enhancer-2 (PSENEN), nicastrin, and anterior pharynx defective 1 (APH1). To date, 57 mutations of γ-secretase genes have been reported in 70 patients or families worldwide, including 39 in NCSTN, 14 in PSENEN, and 4 in PSEN1, of which 17 are frameshifts, 15 result in nonsense mutations, 13 in missense mutations, and 12 are splice site mutations. Given the structure of γ-secretase and analysis of related mutation loci of NCSTN, PSENEN, and PSEN1, mutations in γ-secretase genes could affect activation of presenilin, prevent substrate binding, and hinder intramembrane cleavage of select proteins. The Author(s). Published by S. Karger AG, Basel.
Authors: Pearl P Y Lie; Lang Yoo; Chris N Goulbourne; Martin J Berg; Philip Stavrides; Chunfeng Huo; Ju-Hyun Lee; Ralph A Nixon Journal: Sci Adv Date: 2022-04-29 Impact factor: 14.957