Title:Role of SIRT-1 as a Target for Treatment and Prevention of Diabetic
Nephropathy: A Review
Volume: 16
Author(s): Anita Kumari, Nalini Sodum, Velayutham Ravichandiran and Nitesh Kumar*
Affiliation:
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Hajipur, Vaishali-844102, Bihar, India
Keywords:
Diabetic nephropathy, SIRT1, NAD+, insulin, Nrf2 pathway, NF-κB pathway, FoxO1, VEGF, regeneration, p53, oxidative stress, TAK-1, clinical relevance, transcription factors.
Abstract: Type-2 diabetes mellitus is a prime factor for the development of Diabetic Nephropathy
(DN) that affects the vital organ namely the kidneys, and further alters the functions of the
nephron system. DN is nowadays becoming a challenge for scientists towards the world because
of its high pervasiveness and complexity of medication. Various risk factors are involved
in the initiation of pathogenic DN, which are associated with different pathways against drug
activity. Due to this DN becomes an unpredictable query to the researchers. SIRT1 is a silent
information regulator factor 2 related enzyme 1 (SIRT1) is nicotinamide adenine dinucleotide
(NAD+) dependent deacetylase that functions as an intracellular regulator of transcriptional activity.
An activated version of SIRT-1 improves the metabolic diseased conditions associated
with other molecular pathways. SIRT1 attenuates diabetic nephropathy in in vitro and in vivo
experimental models of diabetes containing Podocytes, Mesangial cells, and Renal proximal
tubular cells. SIRT1 shows nephroprotective effects in DN in part through deacetylation of
transcription factors i.e., imply in the disease like p53, PTP1B, FOXO, RelA, NF- kβ, STAT-3,
and PGC-1α/ PPARγ. It has been shown that some natural products like resveratrol and synthetic
compounds are activating the SIRT1, this further involved the cascade pathways to prevent
the DN. This review will help regarding the effectiveness of SIRT1as target in the prevention
and treatment of DN.