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LncRNAs as putative biomarkers and therapeutic targets for Parkinson’s disease

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Abstract

Parkinson’s disease (PD) is known as one of the most common degenerative disorders related to the damage of the central nervous system (CNS). This brain disorder is also characterized by the formation of Lewy bodies in the cytoplasm of the dopaminergic neurons in the substantia nigra pars compacta (SNc), which consequently leads to motor and non-motor symptoms. With regard to the growing trend in the number of cases with PD and its effects on individuals, families, and communities, immediate treatments together with diagnostic methods are required. In this respect, long non-coding ribonucleic acids (lncRNAs) represent a large class of ncRNAs with more than 200 nucleotides in length, playing key roles in some important processes including gene expression, cell differentiation, genomic imprinting, apoptosis, and cell cycle. They are highly expressed in the CNS and previous studies have further reported that the expression profile of lncRNAs is disrupted in human diseases such as neurodegenerative disorders. Since the levels of some lncRNAs change over time in the brains of patients with PD, a number of previous studies have examined their potentials as biomarkers for this brain disorder. Therefore, the main purpose of this study was to review the advances in the related literature on lncRNAs as diagnostic, therapeutic, and prognostic biomarkers for PD.

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Fig. 1

adapted from Ying Lyu et al. (2019). The functions of lncRNAs involved in the regulation of several processes at different levels, including (1) transcription, (2) post-transcription, and (3) interaction with other biological molecules

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Abbreviations

PD:

Parkinson’s disease

CNS:

Central nervous system

SNc:

Substantia nigra pars compacta

SNCA:

Alpha-synuclein

LRRK2:

Leucine-rich repeat kinase 2

RNA:

Ribonucleic acid

lncRNA:

Long non-coding RNA

HD:

Huntington’s disease

AD:

Alzheimer’s disease

NEAT1:

Nuclear enriched assembly transcript 1

SNHG1:

Small nucleolar RNA host gene 1

HTR2A:

5-Hydroxytryptamine receptor 2A

NOD:

Nucleotide-binding domain

UCA1:

Urothelial carcinoma-associated 1

MALAT1:

Metastasis-associated lung adenocarcinoma transcript 1

lincRNA-p21:

Long intergenic non-coding RNA p21

HIF1α:

Hypoxia-inducible factor 1 subunit alpha

linc-POU3F3:

Long intergenic non-coding RNA POU3F3

L1CAM:

L1 cell adhesion molecule

GCase:

Glucocerebrosidase

miR-15a-5p:

MicroRNA-15a-5p

C57BL/6:

C57 black 6

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

CASP3:

Caspase-3

NGF:

Neuronal growth factor

BDNF:

Brain-derived neurotrophic factor

IL-1β:

Interleukin 1 beta

TNF-α:

Tumor necrosis factor alpha

PI3K:

Phosphatidylinositol 3-kinase;

AKT:

Protein kinase B

IκBα:

Inhibitor of nuclear factor kappa B

UCHL1:

Ubiquitin carboxy-terminal hydrolase L1

NURR1:

Nuclear receptor-related 1 protein

AS:

Antisense

BACE1:

β-Site amyloid precursor protein cleaving enzyme 1

iNOS:

Inducible nitric oxide synthase

MAP1LC3:

Microtubule-associated protein 1 light chain 3

PINK1:

PTEN-induced kinase 1

ATP:

Adenosine triphosphate

ROS:

Reactive oxygen species

LDH:

Lactate dehydrogenase

SOD:

Superoxide dismutase

RNAi:

RNA interference

ASO:

AS oligonucleotide

HOTAIR:

HOX transcript AS intergenic RNA

NLRP3:

NOD-like receptor protein 3

N2a:

Neuro 2A

NRF2:

Nuclear factor (erythroid-derived 2)-like-2 factor

EZH2:

Enhancer of zeste homolog 2

PRC2:

Polycomb repressive complex 2

LRRK2:

Leucine-rich repeat kinase

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Authors and Affiliations

  1. Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Eskandar Taghizadeh & Alihossein Saberi

  2. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

    Eskandar Taghizadeh

  3. Department of Biotechnology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Seyed Mohammad Gheibihayat

  4. Islamic Azad University (Shahrekord Branch), Shahrekord, Iran

    Forough Taheri

  5. Department of Cardiology, Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Seyed Mohammadreza Afshani

  6. Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran

    Najmeh Farahani

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  1. Eskandar Taghizadeh
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  2. Seyed Mohammad Gheibihayat
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  3. Forough Taheri
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Idea development: Eskandar Taghizadeh; literature search: Eskandar Taghizadeh and Forough Taheri; drafting: Seyed Mohammad Gheibihayat and Mohammadreza Afshani; critical revisions: Alihossein Saberi.

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Taghizadeh, E., Gheibihayat, S.M., Taheri, F. et al. LncRNAs as putative biomarkers and therapeutic targets for Parkinson’s disease. Neurol Sci 42, 4007–4015 (2021). https://doi.org/10.1007/s10072-021-05408-7

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