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Polyphenols Targeting MAP Kinase Signaling Pathway in Neurological Diseases: Understanding Molecular Mechanisms and Therapeutic Targets

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Abstract

Polyphenols are a class of secondary metabolic products found in plants that have been extensively studied for how well they regulate biological processes, such as the proliferation of cells, autophagy, and apoptosis. The mitogen-activated protein kinase (MAPK)-mediated signaling cascade is currently identified as a crucial pro-inflammatory pathway that plays a significant role in the development of neuroinflammation. This process has been shown to contribute to the pathogenesis of several neurological conditions, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), CNS damage, and cerebral ischemia. Getting enough polyphenols through eating habits has resulted in mitigating the effects of oxidative stress (OS) and lowering the susceptibility to associated neurodegenerative disorders, including but not limited to multiple sclerosis (MS), AD, stroke, and PD. Polyphenols possess significant promise in dealing with the root cause of neurological conditions by modulating multiple therapeutic targets simultaneously, thereby attenuating their complicated physiology. Several polyphenolic substances have demonstrated beneficial results in various studies and are presently undergoing clinical investigation to treat neurological diseases (NDs). The objective of this review is to provide a comprehensive summary of the different aspects of the MAPK pathway involved in neurological conditions, along with an appraisal of the progress made in using polyphenols to regulate the MAPK signaling system to facilitate the management of NDs.

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Abbreviations

Aβ:

Amyloid-β

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

HD:

Huntington’s disease

MS:

Multiple sclerosis

αS:

α-Synuclein

PNS:

Peripheral nervous system

ROS:

Reactive oxygen species

CNS:

Central nervous system

NFTs:

Neurofibrillary tangles

NO:

Nitric oxide

ASD:

Autism spectrum disorder

ATF4:

Activating transcription factor 4

BDNF:

Brain-derived neurotrophic factor

BSA:

Bovine serum albumin

COX-2:

Cyclooxygenase-2

EGCG:

Epigallocatechin gallate

ERK:

Extracellular signal-regulated kinase

IL:

Interleukin

JNK:

c-Jun N-terminal kinase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MKP-1:

MAP kinase phosphatase 1

MMP-2:

Matrix metallopeptidase 2

MPTP:

Mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NF-κB:

Nuclear factor kappa-B

NR:

Normal dongjin rice

OS:

Oxidative stress

OA:

Okadaic acid

PGE2:

Prostaglandin E2

RR:

Resveratrol-enriched rice

iNOS:

Inducible nitric oxide synthase

SN:

Substantia nigra

6-OHDA:

6-Hydroxydopamine

COMT:

Catechol-O-methyl transferase

AChE:

Acetylcholinesterase

SOD:

Superoxide dismutase

STAT3:

Signal transducer and activator of transcription 3

TLR4:

Toll-like receptor 4

TNF-α:

Tumor necrosis factor-α

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Funding

The authors express their gratitude to the Deanship of Scientific Research at King Khalid University for funding this work through the Large Research Group Project under grant number RGP.02/339/44.

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Author notes

  1. Fahadul Islam, Sumon Roy and Mehrukh Zehravi contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh

    Fahadul Islam & Talha Bin Emran

  2. Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh

    Sumon Roy, Shyamjit Paul & Hriday Sutradhar

  3. Department of Clinical Pharmacy, College of Dentistry & Pharmacy, Buraydah Private Colleges, Buraydah, 51418, Kingdom of Saudi Arabia

    Mehrukh Zehravi

  4. Department of Pharmacology, Seven Hills College of Pharmacy, Tirupati, India

    Lavanya Yaidikar

  5. Department of Pharmaceutical Analysis, Moonray Institute of Pharmaceutical Sciences, Raikal (V), Farooq Nagar (Tlq), Shadnagar (M), R.R Dist., Telangana, 501512, India

    B. Raj Kumar

  6. Department of Pharmacognosy, MB School of Pharmaceutical Sciences, MBU, Tirupati, Andhra Pradesh, India

    Lakshman Kumar Dogiparthi

  7. Crescent School of Pharmacy, BS Abdur Rahman Crescent Institute of Science and Technology, Vandalur, Chennai, 600048, India

    S. Prema

  8. Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, 90245, Indonesia

    Firzan Nainu

  9. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia

    Safia Obaidur Rab

  10. Faculty of Nature and Life Sciences, University of Ibn Khaldoun-Tiaret, Tiaret, Algeria

    Koula Doukani

  11. Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI, 02912, USA

    Talha Bin Emran

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  1. Fahadul Islam
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Contributions

FI: conceptualization; data curation; formal analysis; investigation; methodology; resources; software; supervision; visualization; roles/writing—original draft; writing—review and editing. SR: data curation; investigation; methodology; resources; software; roles/writing—original draft; writing—review and editing. MZ: data curation; investigation; methodology; resources; software; roles/writing—original draft; writing—review and editing; supervision. SPa: data curation; investigation; methodology; resources; software; roles/writing—original draft; writing—review and editing. HS: data curation; investigation; methodology; resources; software; roles/writing—original draft; writing—review and editing. LY: formal analysis; investigation; validation; visualization; roles/writing—review and editing. BRK: formal analysis; investigation; validation; visualization; roles/writing—review and editing. LKD: formal analysis; investigation; validation; visualization; roles/writing—review and editing. SPr: formal analysis; investigation; validation; visualization; roles/writing—review and editing. FN: formal analysis; investigation; validation; visualization; roles/writing—review and editing. SOR: formal analysis; investigation; validation; visualization; roles/writing—review and editing. KD: formal analysis; investigation; validation; visualization; roles/writing—review and editing. TBE: conceptualization; formal analysis; funding acquisition; investigation; methodology; project administration; supervision; validation; visualization; writing—review and editing.

Corresponding authors

Correspondence to Mehrukh Zehravi or Talha Bin Emran.

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Islam, F., Roy, S., Zehravi, M. et al. Polyphenols Targeting MAP Kinase Signaling Pathway in Neurological Diseases: Understanding Molecular Mechanisms and Therapeutic Targets. Mol Neurobiol 61, 2686–2706 (2024). https://doi.org/10.1007/s12035-023-03706-z

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