TY - JOUR
T1 - From Acid Alpha-Glucosidase Deficiency to Autophagy
T2 - Understanding the Bases of POMPE Disease
AU - Sánchez-Porras, Valentina
AU - Guevara-Morales, Johana Maria
AU - Echeverri-Peña, Olga Yaneth
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/8/5
Y1 - 2023/8/5
N2 - Pompe disease (PD) is caused by mutations in the GAA gene, which encodes the lysosomal enzyme acid alpha-glucosidase, causing lysosomal glycogen accumulation, mainly in muscular tissue. Autophagic buildup is considered the main factor affecting skeletal muscle, although other processes are also involved. Uncovering how these mechanisms are interconnected could be an approximation to address long-lasting concerns, like the differential skeletal and cardiac involvement in each clinical phenotype. In this sense, a network reconstruction based on a comprehensive literature review of evidence found in PD enriched with the STRING database and other scientific articles is presented. The role of autophagic lysosome reformation, PGC-1α, MCOLN1, calcineurin, and Keap1 as intermediates between the events involved in the pathologic cascade is discussed and contextualized within their relationship with mTORC1/AMPK. The intermediates and mechanisms found open the possibility of new hypotheses and questions that can be addressed in future experimental studies of PD.
AB - Pompe disease (PD) is caused by mutations in the GAA gene, which encodes the lysosomal enzyme acid alpha-glucosidase, causing lysosomal glycogen accumulation, mainly in muscular tissue. Autophagic buildup is considered the main factor affecting skeletal muscle, although other processes are also involved. Uncovering how these mechanisms are interconnected could be an approximation to address long-lasting concerns, like the differential skeletal and cardiac involvement in each clinical phenotype. In this sense, a network reconstruction based on a comprehensive literature review of evidence found in PD enriched with the STRING database and other scientific articles is presented. The role of autophagic lysosome reformation, PGC-1α, MCOLN1, calcineurin, and Keap1 as intermediates between the events involved in the pathologic cascade is discussed and contextualized within their relationship with mTORC1/AMPK. The intermediates and mechanisms found open the possibility of new hypotheses and questions that can be addressed in future experimental studies of PD.
KW - Pompe disease
KW - acid alpha-glucosidase
KW - autophagy
KW - glycogen storage disease type II
KW - interaction network
UR - http://www.scopus.com/inward/record.url?scp=85167906082&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/bfa5a22b-e9d6-3920-93e3-187b7c044db8/
U2 - 10.3390/ijms241512481
DO - 10.3390/ijms241512481
M3 - Article
C2 - 37569856
AN - SCOPUS:85167906082
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 15
M1 - 12481
ER -