Carnosine: A Possible Drug for Vascular Dementia

Kawahara, Dai Mizuno Masahiro

doi:10.4172/2329-6925.1000146

Cited by 3 publications

(1 citation statement)

References 76 publications

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“…It is possible that compounds that regulate metal homeostasis and block amyloid channels may have potential for the treatment of neurodegenerative diseases. Indeed, we found that carnosine attenuates Zn 2+ -induced neurotoxicity [167]. Given that carnosine inhibits oligomerization and attenuates AβP-induced neurotoxicity [168] and PrP106-126-induced neurotoxicity [159], it may have therapeutic potential for amyloid diseases.…”

Section: Discussionmentioning

confidence: 73%

Amyloids: Regulators of Metal Homeostasis in the Synapse

2020

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Conformational changes in amyloidogenic proteins, such as β-amyloid protein, prion proteins, and α-synuclein, play a critical role in the pathogenesis of numerous neurodegenerative diseases, including Alzheimer’s disease, prion disease, and Lewy body disease. The disease-associated proteins possess several common characteristics, including the ability to form amyloid oligomers with β-pleated sheet structure, as well as cytotoxicity, although they differ in amino acid sequence. Interestingly, these amyloidogenic proteins all possess the ability to bind trace metals, can regulate metal homeostasis, and are co-localized at the synapse, where metals are abundantly present. In this review, we discuss the physiological roles of these amyloidogenic proteins in metal homeostasis, and we propose hypothetical models of their pathogenetic role in the neurodegenerative process as the loss of normal metal regulatory functions of amyloidogenic proteins. Notably, these amyloidogenic proteins have the capacity to form Ca2+-permeable pores in membranes, suggestive of a toxic gain of function. Therefore, we focus on their potential role in the disruption of Ca2+ homeostasis in amyloid-associated neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 73%

Amyloids: Regulators of Metal Homeostasis in the Synapse

2020

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Link Between Metal Homeostasis and Neurodegenerative Diseases: Crosstalk of Metals and Amyloidogenic Proteins at the Synapse

Mizuno

Kawahara

2017

Metallomics

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Zinc, Carnosine, and Neurodegenerative Diseases

2018

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Zinc (Zn) is abundantly present in the brain, and accumulates in the synaptic vesicles. Synaptic Zn is released with neuronal excitation, and plays essential roles in learning and memory. Increasing evidence suggests that the disruption of Zn homeostasis is involved in various neurodegenerative diseases including Alzheimer’s disease, a vascular type of dementia, and prion diseases. Our and other numerous studies suggest that carnosine (β-alanyl histidine) is protective against these neurodegenerative diseases. Carnosine is an endogenous dipeptide abundantly present in the skeletal muscles and in the brain, and has numerous beneficial effects such as antioxidant, metal chelating, anti-crosslinking, and anti-glycation activities. The complex of carnosine and Zn, termed polaprezinc, is widely used for Zn supplementation therapy and for the treatment of ulcers. Here, we review the link between Zn and these neurodegenerative diseases, and focus on the neuroprotective effects of carnosine. We also discuss the carnosine level in various foodstuffs and beneficial effects of dietary supplementation of carnosine.

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Carnosine: A Possible Drug for Vascular Dementia

Cited by 3 publications

References 76 publications

Amyloids: Regulators of Metal Homeostasis in the Synapse

Amyloids: Regulators of Metal Homeostasis in the Synapse

Link Between Metal Homeostasis and Neurodegenerative Diseases: Crosstalk of Metals and Amyloidogenic Proteins at the Synapse

Zinc, Carnosine, and Neurodegenerative Diseases

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