Neuroprotective Effects of N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline (NMP) against Amyloid-β-Induced Alzheimer’s Disease Mouse Model

Abstract

Alzheimer’s disease (AD), is a progressive neurodegenerative disorder that involves the deposition of β-amyloid plaques and the clinical symptoms of confusion, memory loss, and cognitive dysfunction. Despite enormous progress in the field, no curative treatment is available. Therefore, the current study was designed to determine the neuroprotective effects of N-methyl-(2S, 4R)-Trans-4-hydroxy-L-proline (NMP) obtained from Sideroxylon obtusifolium, a Brazilian folk medicine with anti-inflammatory and anti-oxidative properties. Here, for the first time, we explored the neuroprotective role of NMP in the Aβ1–42-injected mouse model of AD. After acclimatization, a single intracerebroventricular injection of Aβ1–42 (5 µL/5 min/mouse) in C57BL/6N mice induced significant amyloidogenesis, reactive gliosis, oxidative stress, neuroinflammation, and synaptic and memory deficits. However, an intraperitoneal injection of NMP at a dose of (50 mg/kg/day) for three consecutive weeks remarkably decreased beta secretase1 (BACE-1) and Aβ, activated the astrocyte and microglia expression level as well as downstream inflammatory mediators such as pNF-ĸB, TNF-α, and IL-1β. NPM also strongly attenuated oxidative stress, as evaluated by the expression level of NRF2/HO-1, and synaptic failure, by improving the level of both the presynaptic (SNAP-25 and SYN) and postsynaptic (PSD-95 and SNAP-23) regions of the synapses in the cortexes and hippocampi of the Aβ1–42-injected mice, contributing to cognitive improvement in AD and improving the behavioral deficits displayed in the Morris water maze and Y-maze. Overall, our data suggest that NMP provides potent multifactorial effects, including the inhibition of amyloid plaques, oxidative stress, neuroinflammation, and cognitive deficits.

Novel Findings on CCR1 Receptor in CNS Disorders: A Pathogenic Marker Useful in Controlling Neuroimmune and Neuroinflammatory Mechanisms in Parkinson’s Disease

“…The development of a persistent neuroinflammatory state under pathological settings, such as neurodegenerative illnesses, activated glia and maintained the processes of neuronal degeneration during PD [39]. In this framework, GFAP and IBA-1 expressions were particularly enhanced as a result of the increase in reactive astrocytes and microglia, thus representing trustworthy indicators of brain damage related to neurodegeneration [40].…”

The Role of Oxidative Stress and Natural Products in Maintaining Human Health

“…Five articles revealed the oxidative stress-related mechanisms of the ingredients and extracts derived from herbal medicines or foods via in vivo and in vitro experiments. Jawad et al [16] and Jeong et al [17] highlighted the neuroprotective effects of N-methyl-(2S,4R)-Trans-4-hydroxy-L-proline derived from Sideroxylon obtusifolium and the ethanol extract of Vignae Radiatae Semem, respectively, on Aβ1-42-injected mouse models and neuronal HT22 and microglial BV2 cell lines. The mechanisms underlying these effects involved the alleviation of oxidative stress and a reduction in the generation of reactive oxygen species, respectively.…”