Arginine Reduces Glycation in γ2 Subunit of AMPK and Pathologies in Alzheimer’s Disease Model Mice

Abstract

The metabolism disorders are a common convergence of Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM). The characteristics of AD are senile plaques and neurofibrillary tangles (NFTs) composed by deposits of amyloid−β (Aβ) and phosphorylated tau, respectively. Advanced glycation end−products (AGEs) are a stable modification of proteins by non−enzymatic reactions, which could result in the protein dysfunction. AGEs are associated with some disease developments, such as diabetes mellitus and AD, but the effects of the glycated γ2 subunit of AMPK on its activity and the roles in AD onset are unknown. Methods: We studied the effect of glycated γ2 subunit of AMPK on its activity in N2a cells. In 3 × Tg mice, we administrated L−arginine once every two days for 45 days and evaluated the glycation level of γ2 subunit and function of AMPK and alternation of pathologies. Results: The glycation level of γ2 subunit was significantly elevated in 3 × Tg mice as compared with control mice, meanwhile, the level of pT172−AMPK was obviously lower in 3 × Tg mice than that in control mice. Moreover, we found that arginine protects the γ2 subunit of AMPK from glycation, preserves AMPK function, and improves pathologies and cognitive deficits in 3 × Tg mice. Conclusions: Arginine treatment decreases glycated γ2 subunit of AMPK and increases p−AMPK levels in 3 × Tg mice, suggesting that reduced glycation of the γ2 subunit could ameliorate AMPK function and become a new target for AD therapy in the future.

Chuanxiong Renshen Decoction Inhibits Alzheimer’s Disease Neuroinflammation by Regulating PPARγ/NF-κB Pathway

“…Specific differential metabolite information is shown in Table 1 . In addition L-phenylalanine, 25 , 26 LysoPC(22:0), LysoPC(22:1(13Z)), LysoPC(14:0/0:0), LysoPC(24:1(15Z)) 27 may be related to the anti-AD neuroinflammatory effect of CRD.…”

Amino acid metabolism in health and disease

“…Glycosylation of the AMPK-γ subunit inhibits AMPK function, and arginine treatment protects AMPK-γ from glycosylation and increases AMPK phosphorylation in a mouse model of AD, thereby ameliorating AD disease. 215 In patients with mild AD/cognitive impairment (MCI), a combination of L-arginine, HMG-CoA inhibitor simvastatin, and tetrahydrobiopterin to enhance the endothelial nitric oxide synthase (eNOS) pathway modestly increases cerebral blood flow and improves cognition. 216 In addition, PRMT4-catalyzed asymmetric dimethylarginine (ADMA) has been reported to bind to NOS as a ligand, leading to NOS dysfunction, resulting in decreased cerebral blood flow and aggravating AD, which can be reversed by inhibition of PRMT4.…”

The Reduced Gray Matter Volume and Functional Connectivity of the Cerebellum in Type 2 Diabetes Mellitus with High Insulin Resistance

“…Insulin resistance can lead to various central symptoms, including cognitive impairment and emotional decline, negatively affecting the brain [5,7]. Recently, T2DM is considered a risk factor for Alzheimer's disease [8,9], and T2DM with high blood glucose increased the risk of dementia by 40% [8]. Accordingly, it is highly conceivable that insulin resistance may represent a shared pathological mechanism for the progression of both T2DM and Alzheimer's disease [4,7], underscoring the importance of recognizing and improving insulin resistance in T2DM as a potential avenue for early intervention in Alzheimer's disease [10].…”