Human BACE1 blocking peptide

Amyloid-beta (A beta) plays a critical role in the pathogenesis of Alzheimer's disease (AD), an age-related neurode-generative ailment. Emerging evidence suggests that Tenuifolin (TEN) significantly decreases A beta secretion and relieves cellular inflammatory responses. However, the mechanism of this activity has not been fully elucidated. In the present study, we investigate the effect of TEN on autophagy, a process that plays an important role in the generation and metabolism of A beta, in the presence or absence of the autophagy inhibitor 3-MA. The obtained results show that TEN prevents A beta 25-35-induced inflammation and decreases A beta 1-40 and A beta 1-42 levels by decreasing BACE1 in SH-SY5Y cells. Moreover, TEN decreases the mRNA levels of BACE1 but has no impact on the gene expressions of amyloid precursor proteins (APP). 3-MA, the most widely used autophagy inhibitor, reverses the effects of TEN in A beta 25-35-induced SH-SY5Y cells. The association between TEN and autophagy was further investigated by examining the levels of autophagy markers LC3 II and Beclin 1, as well as the protein levels of mTOR, AMPK, and ULK1. The results showed that TEN increases LC3 II, Beclin 1, and mTOR, inhibits the degradation of AMPK, and increases the expression of ULK1. This suggests that TEN protects against A beta 25-35-induced cellular inflammation in an AD cell model through the regulation of autophagy, which, in part, is mediated by the activation of the AMPK/mTOR/ULK1 pathway.

Just as multiple sclerosis (MS) has long been primarily considered a white matter (WM) disease, Alzheimer's disease (AD) has for decades been regarded only as a grey matter disorder. However, convergent evidences have suggested that WM abnormalities are also important components of AD, at the same extent as axonal and neuronal loss is critically involved in MS pathophysiology since early clinical stages. These observations have motivated a more thorough investigation about the possible mechanisms that could link neuroinflammation and neurodegeneration, focusing on amyloid-beta (A beta). Neuroimaging studies have found that patients with AD have widespread WM abnormalities already at the earliest disease stages and prior to the presence of A beta plaques. Moreover, a correlation between cerebrospinal fluid (CSF) A beta levels and WM lesion load was found. On the other hand, recent studies suggest a predictive role for CSF A beta levels in MS, possibly due in the first instance to the reduced capacity for remyelination, consequently to a higher risk of WM damage progression, and ultimately to neuronal loss. We undertook a review of the recent findings concerning the involvement of CSF A beta levels in the MS disease course and of the latest evidence of AD related WM abnormalities, with the aim to discuss the potential causes that may connect WM damage and amyloid pathology.