Sirtuin Modulation as Novel Neuroprotective Strategy for Alzheimer’s Disease

Alzheimer’s disease (AD) is expected to have a deep impact on health systems due to the lack of an effective therapy and its chronic progression. In search of novel strategies for AD, a very promising field has come to light: sirtuins. Sirtuins (SIRTs) are evolutionary conserved enzymes with deacetylase activity involved in a plethora of basic metabolic functions. In mammals, we find seven sirtuins (SIRT1–7) and mostly thanks to recent details about the molecular targets of SIRT1, SIRT2, and SIRT3 the possibility of discovering novel neuroprotective therapeutic strategies for AD has increased. A great advantage of SIRTs is that they are an ideal small drug target both for activators and inhibitors. However, several issues have to be solved, including the availability of small drugs that are able to cross the blood–brain barrier and the elucidation of the exact pathway linking a specific sirtuin with downstream effects. In this chapter, we summarize current knowledge on SIRTs’ with a focus on their pharmacological modulation as potential strategy in AD neuroprotection.