Natural Sirtuin Modulators in Drug Discovery: A Review (2010 -2020).

There have been intense research interests in sirtuins since the establishment of their regulatory roles in a myriad of pathological processes. In the last two decades, many research efforts have been dedicated to the development of sirtuin modulators. Although synthetic sirtuin modulators are the focus, natural modulators remain an integral part to be further explored in this area as they are found to possess therapeutic potential in various diseases, including cancers, neurodegenerative diseases, and metabolic disorders. Owing to the importance of this cluster of compounds, this review gives a current stand on the naturally occurring sirtuin modulators, associated molecular mechanisms, and their therapeutic benefits. Furthermore, comprehensive data mining resulted in detailed statistical data analysis pertaining to the developmental trend of sirtuin modulators from 2010-2020. Lastly, the challenges and future prospects of natural sirtuin modulators in drug discovery will also be discussed.

Sirtuins and Their Implications in Neurodegenerative Diseases from a Drug Discovery Perspective.

Sirtuins are class III histone deacetylase (HDAC) enzymes that target both histone and non-histone substrates. They are linked to different brain functions and the regulation of different isoforms of these enzymes is touted to be an emerging therapy for the treatment of neurodegenerative diseases (NDs), including Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). The level of sirtuins affects brain health as many sirtuin-regulated pathways are responsible for the progression of NDs. Certain sirtuins are also implicated in aging, which is a risk factor for many NDs. In addition to SIRT1-3, it has been suggested that the less studied sirtuins (SIRT4-7) also play critical roles in brain health. This review delineates the role of each sirtuin isoform in NDs from a disease centric perspective and provides an up-to-date overview of sirtuin modulators and their potential use as therapeutics in these diseases. Furthermore, the future perspectives for sirtuin modulator development and their therapeutic application in neurodegeneration are outlined in detail, hence providing a research direction for future studies.