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Disease-modifying treatment of Parkinson’s disease by phytochemicals: targeting multiple pathogenic factors

  • Neurology and Preclinical Neurological Studies - Review Article
  • Published:
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Abstract

Parkinson’s disease is characterized by typical motor symptoms, loss of dopamine neurons in the substantia nigra, and accumulation of Lewy body composed of mutated α-synuclein. However, now it is considered as a generalized disease with multiple pathological features. Present available treatments can ameliorate symptoms at least for a while, but only a few therapies could delay progressive neurodegeneration of dopamine neurons. Lewy body accumulates in peripheral tissues many years before motor dysfunction becomes manifest, suggesting that disease-modifying therapy should start earlier during the premotor stage. Long-termed regulation of lifestyle, diet and supplement of nutraceuticals may be possible ways for the disease-modification. Diet can reduce the incidence of Parkinson’s disease and phytochemicals, major bioactive ingredients of herbs and plant food, modulate multiple pathogenic factors and exert neuroprotective effects in preclinical studies. This review presents mechanisms underlying neuroprotection of phytochemicals against neuronal cell death and α-synuclein toxicity in Parkinson’s disease. Phytochemicals are antioxidants, maintain mitochondrial function and homeostasis, prevent intrinsic apoptosis and neuroinflammation, activate cellular signal pathways to induce anti-apoptotic and pro-survival genes, such as Bcl-2 protein family and neurotrophic factors, and promote cleavage of damaged mitochondria and α-synuclein aggregates. Phytochemicals prevent α-synuclein oligomerization and aggregation, and dissolve preformed α-synuclein aggregates. Novel neuroprotective agents are expected to develop based on the scaffold of phytochemicals permeable across the blood–brain–barrier, to increase the bioavailability, ameliorate brain dysfunction and prevent neurodegeneration.

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Abbreviations

ARE:

Antioxidant responsive element

ALP:

Autophagy-lysosome pathway

αSyn:

α-Synuclein

GCase:

Glucocerebrosidase

HMGB1:

High-mobility group box 1

MMP:

Mitochondrial membrane permeabilization

mPTP:

Mitochondrial permeability transition pore

RPCT:

Randomized, placebo-controlled trial

TSPO:

The outer membrane translocator protein 18 kDa

UPDRS:

Unified Parkinson’s Disease Rating Scale

UPS:

Ubiquitin–proteasome system

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Funding

The authors’ research of food-derived bioactive compounds is supported by the Grants-in-Aids for Scientific Research, No. 18Kk07430 (WM).

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  1. Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 320-0195, Japan

    Makoto Naoi, Wakako Maruyama & Masayo Shamoto-Nagai

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  1. Makoto Naoi
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  2. Wakako Maruyama
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  3. Masayo Shamoto-Nagai
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Correspondence to Makoto Naoi.

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Naoi, M., Maruyama, W. & Shamoto-Nagai, M. Disease-modifying treatment of Parkinson’s disease by phytochemicals: targeting multiple pathogenic factors. J Neural Transm 129, 737–753 (2022). https://doi.org/10.1007/s00702-021-02427-8

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