They observed a sign ificant increase in the concen trationof brain sAPP levels in CR animals compared to con trols. There also appeared to be a moderate increase in levels of the insulin degrading enzyme, which has been associated with brain amy loid clearance. The potential link between RESV and AD is also supported by studies which suggest that moderate consumption ofwine is associatedwith a lower incidenceof AD and improved neuropathology in a mouse model of the disease. More interestingly, RESV can rescuehippocampal primary neurons and PC cells from the tox icity of. Thus, a reasch L-α-Phosphatidylcholine treatmentwith RESV, admin istrated haf ter the amy loid peptideinduced cell death in a concentrationdependent manner. As regards the other potential pathways involved in RESV neuroprotection against amylo id, research has demonstrated the role of PKC activity in th is effect.In contrast, studies in SHSYY neuroblastoma cells showed that RESV can induce the activation of the MAP kinases, ERK and ERK. In addition to these signalling pathways, RESV can also induce the expression of the transcr iption factor early growth response. These resu lts suggest that RESV can activate the proteasome involved in the degradation of the amyloid peptide.The majorities of them suffer from a sporad ic form, and although the genetic causes are fairly well identified the reasons for the emergence of these sporadic forms remains unclear. The involvementof mitochondrial dysfunction in PD has been established for over two decades, since it was discovered that the admin istration of methy lphenyl, tetrahydropyridine causes the emergenceof parkinsonism in both laboratory animals and humans through its active metabo lite ion MPP, which inh ibits complex I in the chain of mitochondrial electron transfer. Complex I inh ibition is known to be the major source of free radicals, and it is thought that the alteration in its functions cou ld, above and beyond the declin ing production of ATP, give rise to increased oxidative stress, thus explaining the emergenceof thedisease. Previous in vivo stud ies suggest that RESV exerts beneficial effects in exper imental models of PD. For example, the administration of a diet con taining RESV or treatmentwith RESV to adu lt mice pr ior to treatment with the neurotox in MPTP exerts neuroprotective effects on dopaminergic neurons. Furthermore, in vitro studies have also demonstrated the neuroprotective effects of RESV with different neurotoxins. However, it has been suggested that SIRT activation does not play a major role in the protective effect of RESV against MPP cyto toxicity, because sirtuin inhib itors such asnicotinamide and sirtinol did not counteract neuroprotection by RESV. In contrast, all studies in th is area propose that antiox idant actions are responsib le for the neuroprotection by RESV against MPP. However, there are recentreports that genetic inhibition of SIRT via small in terfering RNA rescued synuclein toxicity.According ly, RESV could be an interesting candidate for potential application in the treatment of PD, although probably only on the basis of its antioxidantproperties; at presentit remains to be clarif ied if RESV could activates SIRT and offers neuroprotection in PD.