Background: Tripeptide Met-Lys-Pro (MKP), a component of casein hydrolysates, has effective angiotensin-converting enzyme (ACE) inhibitory activity. Brain angiotensin II enzyme activates the NADPH oxidase complex via angiotensin II receptor type 1 (AT1) and enhances oxidative stress injury. ACE inhibitors improved cognitive function in Alzheimer's disease (AD) mouse models and previous clinical trials. Thus, although undetermined, MKP may be effective against pathological amyloid-β (Aβ) accumulation-induced cognitive impairment.
Objective: The current study aimed to investigate the potential of MKP as a pharmaceutical against AD by examining MKP's effect on cognitive function and molecular changes in the brain using double transgenic (APP/PS1) mice.
Methods: Experimental procedures were conducted in APP/PS1 mice (n = 38) with a C57BL/6 background. A novel object recognition test was used to evaluate recognition memory. ELISA was used to measure insoluble Aβ40, Aβ42, and TNF-α levels in brain tissue. Immunohistochemical analysis allowed the assessment of glial cell activation in MKP-treated APP/PS1 mice.
Results: The novel object recognition test revealed that MKP-treated APP/PS1 mice showed significant improvement in recognition memory. ELISA of brain tissue showed that MKP significantly reduced insoluble Aβ40, Aβ42, and TNF-α levels. Immunohistochemical analysis indicated the suppression of the marker for microglia and reactive astrocytes in MKP-treated APP/PS1 mice.
Conclusion: Based on these results, we consider that MKP could ameliorate pathological Aβ accumulation-induced cognitive impairment in APP/PS1 mice. Furthermore, our findings suggest that MKP potentially contributes to preventing cognitive decline in AD.
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http://dx.doi.org/10.3233/JAD-220192 | DOI Listing |
Pharmaceuticals (Basel)
January 2025
School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.
Alzheimer's disease (AD) is the leading cause of dementia among the elderly, yet effective treatments remain elusive. Total saikosaponins (TSS), the primary bioactive components in , have shown promising therapeutic effects against AD in previous studies. : To delve deeper into the mechanisms underlying the therapeutic role of TSS in AD, we investigated its neuroprotective effects and associated molecular mechanisms in APP/PS1 mice.
View Article and Find Full Text PDFAnal Chem
January 2025
Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, China.
A rapid, sensitive, and high-throughput sample preparation method is of paramount significance for proteomics analysis. Here, we report a fast, high-sensitivity MICROFASP method that is capable of completing sample preparation within 1.5 h, enhancing the throughput by over 13 times compared to the previous reports.
View Article and Find Full Text PDFStem Cell Res Ther
January 2025
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, International Center for Technology and Innovation of Animal Model, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, 100021, China.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative condition affecting around 50 million people worldwide. Bone marrow-derived mesenchymal stem cells (BMMSCs) have emerged as a promising source for cellular therapy due to their ability to differentiate into multiple cell types and their paracrine effects. However, the direct injection of BMMSCs can lead to potential unpredictable impairments, prompting a renewed interest in their paracrine effects for AD treatment.
View Article and Find Full Text PDFPhytomedicine
January 2025
Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address:
People with mild cognitive impairment (MCI) carry a considerable risk of developing dementia. Studies have shown that female sex hormones have long-lasting neuroprotective and anti-aging properties, and the increased risk of MCI and AD is associated with the lack of estrogen during menopause. Previous studies have shown that Tiao Geng Decoction (TGD) may have antioxidant and anti apoptotic properties, which may prevent neurodegenerative diseases.
View Article and Find Full Text PDFMol Nutr Food Res
January 2025
Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China.
Scope: Alzheimer's disease (AD) is the most prevalent form of dementia, lack of effective therapeutic interventions. In this study, we investigate the impact of intermittent fasting (IF), an alternative strategy of calorie restriction, on cognitive functions and AD-like pathology in a transgenic mouse model of AD.
Methods And Results: APP/PS1 mice at 6 months were randomly allocated to two dietary groups: one receiving ad libitum (AL) feeding and the other undergoing IF for 1 month.
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