Carnisone Increases Efficiency of DOPA Therapy of Parkinson's Disease: A Pilot Study

Boldyrev, Alexander A.; Федорова, Т. Н.; Stepanova, Maria; Dobrotvorskaya, Irina S.; Козлова, Е. В.; Болданова, Н. Б.; Bagyeva, G. Kh.; Ivanova-Smolenskaya, I. A.; Иллариошкин, С. Н.

doi:10.1089/rej.2008.0716

Cited by 104 publications

(69 citation statements)

References 18 publications

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“…The unexpected role of anticonvulsants as anti-ageing agent, at least in nematodes, and the association of carnosine/homocarnosine with anticonvulsant activity in rodents and humans are further testament to the enigmatic pluripotency of this almost non-toxic peptide. Possible beneficial effects of the dipeptide on agerelated pathologies such as diabetes (Hipkiss, 2005(Hipkiss, & 2006c, Alzheimer's disease (Hipkiss, 2007c), Parkinsons's disease (Boldyrev et al, 2008) and stroke (Dobrota et al, 2005) have therefore been proposed.…”

Section: Discussionmentioning

confidence: 99%

On the enigma of carnosine’s anti-ageing actions

Hipkiss¹

2009

Experimental Gerontology

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Carnosine ( -alanyl-L-histidine) has described as a forgotten and enigmatic dipeptide. Carnosine's enigma is particularly exemplified by its apparent anti-ageing actions; it suppresses cultured human fibroblast senescence and delays ageing in senescence-accelerated mice and Drosophila, but the mechanisms reponsible remain uncertain. In addition to carnosine's well-documented anti-oxidant, anti-glycating, aldehyde-scavenging and toxic metal-ion chelating properties, its ability to influence the metabolism of altered polypeptides, whose accumulation characterises the senescent phenotype, should also be considered. When added to cultured cells, carnosine was found in a recent study to suppress phosphorylation of the translational initiation factor eIF4E resulting in decreased translation frequency of certain mRNA species. Mutations in the gene coding for eIF4E in nemtodes extend organism lifespan, hence carnosine's anti-ageing effects may be a consequence of decreased error-protein synthesis which in turn lowers formation of protein carbonyls and increases protease availability for degradation of polypeptides altered postsynthetically. Other studies have revealed carnosine-induced upregulation of stress protein expression and nitric oxide synthesis, both of which may stimulate proteasomal elimination of altered proteins. Some anti-convulsants can enhance nematode longevity and suppress the effects of a protein repair defect in mice, and as carnosine exerts anti-convulsant effects in rodents, it is speculated that the dipeptide may participate in the repair of protein isoaspartyl groups. These new observations only add to the enigma of carnosine's real in vivo functions. More experimentation is clearly required. ACCEPTED MANUSCRIPT 3 Carnosine and ageing.The naturally-occurring dipeptide carnosine ( -alanyl-L-histidine) has been described as forgotten and enigmatic (Bauer, 2005): the present paper is an attempt to rectify the former opinion, but, however only adds to the latter view. Amongst carnosine's enigmatic properties are its apparent anti-ageing actions; the dipeptide is one of a very few naturally-occurring compounds which suppresses cell senescence, induces rejuvenating effects Holliday, 1994 and, and protects against telomere shortening (Shao et al., 2004) in cultured human fibroblasts. The dipeptide also extends the life-span of senescence-accelerated mice (Yuneva et al., 1999) and Drosophila (Yuneva et al., 2002). There are many possible mechanisms by which carnosine exerts these anti-ageing actions however, some of which were summarized a decade ago (Hipkiss, 1998). Meanwhile there have been a number of publications suggesting further possible routes by which carnosine could suppress

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Section: Discussionmentioning

confidence: 99%

On the enigma of carnosine’s anti-ageing actions

Hipkiss¹

2009

Experimental Gerontology

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“…Nevertheless, high levels of carnosine and related histidyl peptides (anserine, homocarnosine) are also present in aerobic tissues such as the heart and the brain, suggesting that carnosine might have other functions as well. Previous studies have shown that carnosine protects against ischemic injury (24 -26), hyperglycemia (27), neurodegenerative diseases (28), and aging (29,30). Collectively, these findings indicate that in addition to buffering intracellular pH, carnosine might have an antioxidant role in removing aldehydes (31).…”

mentioning

confidence: 99%

Role of Aldose Reductase in the Metabolism and Detoxification of Carnosine-Acrolein Conjugates

Baba

Hoetker

Merchant

et al. 2013

Journal of Biological Chemistry

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Background: Lipid peroxidation generates unsaturated aldehydes that form conjugates with histidyl dipeptides. Results: Carnosine-aldehyde conjugates form covalent adducts with proteins and are reduced by aldose reductase. Conclusion: Detoxification of carnosine-aldehyde by aldose reductase prevents protein carnosinylation. Significance: Aldose reductase prevents tissue injury due to aldehyde-carnosine conjugates.

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“…As previously discussed, carnosine counteracts MG and other cytotoxic aldehydes [50], which in part could substantiate its neuroprotective effect in PD patients. A pilot study performed by Boldyrev and colleagues [99] assessed the efficacy of carnosine (1.5 g, daily, by 30 days) as a complement to DOPA drug therapy in PD patients. It was concluded that the combination of carnosine with basic therapy for certain PD patients may be a reasonable way to improve the protocol of PD treatment and to decrease the possible toxic effects of the overloading of DOPA-containing drugs [99].…”

Section: Parkinson's Disease (Pd)mentioning

confidence: 99%

“…A pilot study performed by Boldyrev and colleagues [99] assessed the efficacy of carnosine (1.5 g, daily, by 30 days) as a complement to DOPA drug therapy in PD patients. It was concluded that the combination of carnosine with basic therapy for certain PD patients may be a reasonable way to improve the protocol of PD treatment and to decrease the possible toxic effects of the overloading of DOPA-containing drugs [99]. Due to the small number of volunteers and the short duration of this study, a larger and long-term trial is needed to confirm the benefit of carnosine combined to DOPA drug therapy.…”

Section: Parkinson's Disease (Pd)mentioning

confidence: 99%

Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders

Cararo¹,

Streck²,

Schuck³

et al. 2015

Aging and disease

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Imidazole dipeptides (ID), such as carnosine (β-alanyl-L-histidine), are compounds widely distributed in excitable tissues of vertebrates. ID are also endowed of several biochemical properties in biological tissues, including antioxidant, bivalent metal ion chelating, proton buffering, and carbonyl scavenger activities. Furthermore, remarkable biological effects have been assigned to such compounds in age-related human disorders and in patients whose activity of serum carnosinase is deficient or undetectable. Nevertheless, the precise biological role of ID is still to be unraveled. In the present review we shall discuss some evidences from clinical and basic studies for the utilization of ID as a drug therapy for age-related human disorders.

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Carnisone Increases Efficiency of DOPA Therapy of Parkinson's Disease: A Pilot Study

Cited by 104 publications

References 18 publications

On the enigma of carnosine’s anti-ageing actions

On the enigma of carnosine’s anti-ageing actions

Role of Aldose Reductase in the Metabolism and Detoxification of Carnosine-Acrolein Conjugates

Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders

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