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Natural Compounds as Therapeutic Agents for Amyloidogenic Diseases pp 79–94Cite as

Natural Phenolic Compounds as Therapeutic and Preventive Agents for Cerebral Amyloidosis

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 863))

Abstract

Epidemiological studies have suggested that diets rich in phenolic compounds may have preventive effects on the development of dementia or Alzheimer’s disease (AD). We investigated the effects of natural phenolic compounds, such as myricetin (Myr), rosmarinic acid (RA), ferulic acid (FA), curcumin (Cur) and nordihydroguaiaretic acid (NDGA) on the aggregation of amyloid β-protein (Aβ), using in vitro and in vivo models of cerebral Aβ amyloidosis. The in vitro studies revealed that these phenolic compounds efficiently inhibit oligomerization as well as fibril formation of Aβ through differential binding, whilst reducing Aβ oligomer-induced synaptic and neuronal toxicity. Furthermore, a transgenic mouse model fed orally with such phenolic compounds showed significant reduction of soluble Aβ oligomers as well as of insoluble Aβ deposition in the brain. These data, together with an updated review of the literature, indicate that natural phenolic compounds have anti-amyloidogenic effects on Aβ in addition to well-known anti-oxidative and anti-inflammatory effects, hence suggesting their potential as therapeutic and/or preventive agents for cerebral Aβ amyloidosis, including AD and cerebral amyloid angiopathy (CAA). Well-designed clinical trials or preventive interventions with natural phenolic compounds are necessary to establish their efficacy as disease-modifying agents.

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Abbreviations

Aβ:

amyloid β-protein

AD:

Alzheimer’s disease

ADAS-Cog:

Alzheimer’s Disease Assessment Scale – Cognitive Subscale

αS:

α-synuclein

ApoE:

apolipoprotein E

APP:

amyloid-β precursor protein

CAA:

cerebral amyloid angiopathy

CD:

circular dichroism

CSF:

cerebrospinal fluid

Cur:

curcumin

DLB:

dementia with Lewy bodies

EGCG:

(−)-epigallocatechin-3-galate

FA:

ferulic acid

fAβ:

Αβ fibrils

GSPE:

grape seed polyphenolic extract

LTD:

long-term depression

LTP:

long-term potentiation

MCI:

mild cognitive impairment

MMSE:

Mini-Mental State Examination

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine

MTT:

3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

Myr:

myricetin

NDGA:

nordihydroguaiaretic acid

NMR:

nuclear magnetic resonance

PD:

Parkinson’s disease

PHF:

paired helical filament

PICUP:

photo-induced cross-linking of unmodified proteins

RA:

rosmarinic acid

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Acknowledgements

This work is supported in part by a Grain-in-Aid Scientific Research (MY, KO, TH, MN-S) and a grant from the Hokuriku Innovation Cluster for Health Science (MY) from the Science of the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a Grant for Health and Labour Sciences Research (the Amyloidosis Research Committee) from the Ministry of Health, Labour, and Welfare, Japan (MY). The authors thank Ms. Etsuko Tsujiguchi for her excellent secretarial assistance.

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  1. Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, 13-1, Takara-machi, Kanazawa, 920-8640, Japan

    Masahito Yamada M.D., Ph.D., Kenjiro Ono, Tsuyoshi Hamaguchi & Moeko Noguchi-Shinohara

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  1. Masahito Yamada M.D., Ph.D.
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  2. Kenjiro Ono
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  3. Tsuyoshi Hamaguchi
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  4. Moeko Noguchi-Shinohara
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Correspondence to Masahito Yamada M.D., Ph.D. .

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  1. Department of Physiology and Biochemistry, University of Malta, Msida, Malta

    Neville Vassallo

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Yamada, M., Ono, K., Hamaguchi, T., Noguchi-Shinohara, M. (2015). Natural Phenolic Compounds as Therapeutic and Preventive Agents for Cerebral Amyloidosis. In: Vassallo, N. (eds) Natural Compounds as Therapeutic Agents for Amyloidogenic Diseases. Advances in Experimental Medicine and Biology, vol 863. Springer, Cham. https://doi.org/10.1007/978-3-319-18365-7_4

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