Carnosine improves aging‐induced cognitive impairment and brain regional neurodegeneration in relation to the neuropathological alterations in the secondary structure of amyloid beta (Aβ)

Abstract

Aging‐induced proteinopathies, including deterioration of amyloid beta (Aβ) conformation, are associated with reductions in endogenous levels of carnosine and cognitive impairments. Carnosine is a well‐known endogenous antioxidant, which counteracts aging‐induced Aβ plaque formation. The aim of this study was to investigate the effects of exogenous carnosine treatments on aging‐induced changes (a) in the steady‐state level of endogenous carnosine and conformation of Aβ secondary structure in the different brain regions (cerebral cortex, hippocampus, hypothalamus, pons‐medulla, and cerebellum) and (b) cognitive function. Young (4 months) and aged (18 and 24 months) male albino Wistar rats were treated with carnosine (2.0 μg kg−1 day−1; i.t.) or equivalent volumes of vehicle (saline) for 21 consecutive days and were tested for cognition using 8‐arm radial maze test. Brains were processed to assess the conformational integrity of Aβ plaques using Raman spectroscopy and endogenous levels of carnosine were measured in the brain regions using HPLC. Results indicated that carnosine treatments improved the aging‐induced deficits in cognitive function and reduced the β‐sheets in the secondary structure of Aβ protein, as well as mitigating the reduction in the steady‐state levels of carnosine and spine density in the brain regions examined. These results thus, suggest that carnosine can attenuate the aging‐induced: (a) conformational changes in Aβ secondary structure by reducing the abundance of β‐sheets and reductions in carnosine content in the brain regions and (b) cognitive impairment.

Antioxidant and Neuroprotective Effects of Carnosine: Therapeutic Implications in Neurodegenerative Diseases

“…Therefore, this group thought of supplementing aged Wistar rats with carnosine in order to check if it could alleviate age-related phenotypes. The results obtained in this study indicated that carnosine was able to attenuate aging-induced Aβ plaque formation and improve cognitive impairment in elderly rats [101]. In addition, galactose treatment has been stablished as a model of accelerated aging in rats since it leads to an increase in OS levels.…”

Erythrocytes Prevent Degradation of Carnosine by Human Serum Carnosinase

“…In addition, there is a growing number of consumers using the dipeptide because of its supposed general anti-aging capabilities based on its effects on ROS [ 7 ], which also attracted interest in using it as a component of cosmetic products [ 8 , 9 ]. Protecting against glycating sugars [ 10 ], methylglyoxal [ 11 ], advanced glycation end-products [ 12 ], and amyloid-β peptides [ 13 ], carnosine has also been considered as a therapeutic drug for the treatment of Alzheimer’s disease or cognitive decline in general [ 14 ] and Parkinson’s disease [ 15 ]. Based on experiments performed with cell culture and animal models, carnosine has also been considered as a drug for the treatment of different forms of cancer [ 16 , 17 , 18 , 19 , 20 ] including glioblastoma which is a highly malignant form of brain tumor (for review see [ 21 , 22 ]).…”

Effects of zinc and carnosine on aggregation kinetics of Amyloid-β40 peptide

“…Carnosine is a bioactive molecule that has been indicated to provide protective benefits for counteracting to neurodegenerative conditions [ 30 ]. Recent studies reported that carnosine can inhibit the aggregation of amyloidogenic proteins such as α-crystallin and Aβ42 [ 21 , 31 , 32 ], which may ameliorate the toxicity of protein aggregates.…”