PEN2

Last update 08 May 2025

Basic Info

Synonyms

Gamma-secretase subunit PEN-2, PEN2, Presenilin enhancer protein 2

+ [2]

Introduction

Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:12522139, PubMed:12679784, PubMed:12740439, PubMed:12763021, PubMed:24941111, PubMed:30598546, PubMed:30630874). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable). PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity (PubMed:12522139, PubMed:12679784, PubMed:12740439, PubMed:12763021, PubMed:24941111).

100 Clinical Results associated with PEN2

100 Translational Medicine associated with PEN2

0 Patents (Medical) associated with PEN2

438

Literatures (Medical) associated with PEN2

01 Jun 2025·Current Medicinal Chemistry

Advance of Metformin in Liver Disease

Article

Author: Zhao, Yudi ; Ling, Sunbin ; Xu, Xiao ; Bao, Jiaqi

Metformin is a first-line drug for the treatment of type 2 diabetes with a good safety profile and relatively low cost. In recent years, many other effects of metformin have been discovered. In this review, we provide the research advances in metformin in liver disease. High-dose metformin can activate AMPK by inhibiting mitochondrial complex 1. In addition, low-dose metformin could activate lysosomal AMPK through PEN2. Activated AMPK can reduce fatty acid synthesis, inhibit tumor proliferation and metastasis, and reshape the tumor microenvironment. In addition, metformin can reduce ROS production by inhibiting mitochondrial complex 1, which can reduce liver damage. Therefore, metformin has been found to alleviate nonalcoholic fatty liver disease and cirrhosis, relieve liver damage, and reduce the incidence of hepatocellular carcinoma and cholangiocarcinoma. This information suggests that metformin may represent a new possibility for the prevention and treatment of liver diseases.

01 Apr 2025·Journal of the American Academy of Dermatology

A genome-wide association meta-analysis links hidradenitis suppurativa to common and rare sequence variants causing disruption of the Notch and Wnt/β-catenin signaling pathways

Article

Author: Saemundsdottir, Jona ; Melsted, Pall ; Hjalgrim, Henrik ; Knowlton, Kirk U ; Riis, Peter Theut ; Kjærsgaard Andersen, Rune ; Stefansdottir, Lilja ; Pedersen, Ole Birger Vesterager ; Nyegaard, Mette ; Hansen, Thomas Folkmann ; Ferkingstad, Egil ; Ostrowski, Sisse Rye ; Thorleifsson, Gudmar ; Zachariae, Claus ; Sørensen, Erik ; Dinh, Khoa Manh ; Jemec, Gregor Borut Ernst ; Banasik, Karina ; Halldorsson, Gisli ; Brunak, Søren ; Bruun, Mie Topholm ; Nadauld, Lincoln D ; Orvar, Kjartar B ; Saunte, Ditte Marie Lindhardt ; Jonsdottir, Ingileif ; Walters, Bragi ; Thomsen, Simon Francis ; Brodersen, Thortsen ; Stefansson, Kari ; Stefansson, Hreinn ; Knight, Stacey ; Oddsson, Asmundur ; Mikkelsen, Chirstina ; Sigurgeirsson, Bárdur ; Holm, Hilma ; Gudbjartsson, Daniel ; Sulem, Patrick ; Norddahl, Gudmundur L ; Ullum, Henrik ; Erikstrup, Christian ; Olafsdottir, Thorunn A ; Eidsmo, Liv ; Rutsdottir, Gudrun

BACKGROUNDThe contributions of genetic and environmental risk factors to hidradenitis suppurativa (HS) are both poorly understood.OBJECTIVETo identify sequence variants that associate with HS and determine the contribution of environmental risk factors and inflammatory diseases to HS pathogenesis.METHODSA genome-wide association meta-analysis of 4814 HS cases (Denmark: 1977; Iceland: 1266; Finland: 800; UK: 569; and US: 202) and 1.2 million controls, searching for sequence variants associated with HS.RESULTSWe found 8 independent sequence variants associating with HS, 6 common and 2 rare (frequency <1%). Four associations point to candidate causal genes, NCSTN, PSENEN, WNT10A, and TMED10, that all map to the Notch and Wnt/β-catenin signaling pathways, involved in epidermal keratinization.LIMITATIONSLimited racial diversity may prevent identification of sequence variants of particular importance in non-Caucasian populations.CONCLUSIONSThese findings demonstrate that genes and pathways involved in epidermal keratinization are the genetic backbone of HS pathology.

25 Feb 2025·Journal of Experimental Botany

Arabidopsis METHYLENETETRAHYDROFOLATE REDUCTASE 2 functions independently of PENETRATION 2 during primary immunity against rice blast

Article

Author: Sultan, Eram ; Pati, Debasish ; Sahu, Binod Bihari ; Kumar, Sanjeev

AbstractNon-host resistance (NHR) is the most durable and robust form of innate immunity, with a surge of interest in its role in crop improvement. Of the NHR genes identified against rice blast, a devastating disease caused by Magnaporthe oryzae, Arabidopsis PEN2 is indispensable for pre-penetration resistance to M. oryzae, while a consortium of genes orchestrates post-penetration resistance via lesser known mechanisms. We identified M. oryzae-susceptible mosA (mthfr2 pen2-3) from a randomly mutagenized Arabidopsis pen2-3 population using forward genetics. Analysis of T-DNA-inserted mthfr2 lines and pen2-3-complemented mosA lines revealed that MTHFR2-dependent resistance to M. oryzae is independent of PEN2. MTHFR2-defective plants exhibited higher accumulation of reactive oxygen species and expression of salicylic acid-dependent defense markers. MTHFR2–ligand docking revealed that A55V non-synonymous substitution in mosA altered ligand binding efficiency. This further affected the metabolomic profile of mosA, effectively allowing in vitro germination and development of M. oryzae conidia. Moreover, the loss-of-function mutation in mthfr2 (involved in the 1C metabolic pathway) potentiated mosA immunity against Pst DC3000. In conclusion, our findings showed that MTHFR2 is a positive modulator of NHR against M. oryzae. This work documents another layer of conserved yet divergent metabolomic defense in Arabidopsis regulated by folate-mediated 1C metabolism that has the potential to revolutionize crop improvement.

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PEN2

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