Role of Long Non-coding RNAs in the Pathogenesis of Alzheimer’s and Parkinson’s Diseases

Abstract

Neurodegenerative diseases are a diverse group of diseases that are now one of the leading causes of morbidity in the elderly population. These diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral Sclerosis (ALS), etc. Although these diseases have a common characteristic feature of progressive neuronal loss from various parts of the brain, they have differed in the clinical symptoms and risk factors leading to the development and progression of the diseases. AD is a neurological condition that leads to dementia and cognitive decline due to neuronal cell death in the brain, whereas PD is a movement disorder affecting neuro-motor function and is developed due to the death of the dopaminergic neurons in the brain which results in decreased dopamine levels. Currently, the only treatment available for these neurodegenerative diseases is to reduce the rate of progression of neuronal loss. This necessitates the development of efficient early biomarkers and effective therapies for these diseases. Long non-coding RNAs (LncRNAs) belong to a large family of non-coding transcripts with a minimum length of 200 nucleotides. They are implied in the development of the brain, in a variety of diseases, and epigenetic, transcriptional, and posttranscriptional levels of gene regulation. Aberrant expression of lncRNAs in the CNS is considered to play a major role in the development and progression of AD and PD, two of the most leading cause of morbidity among elderly populations. In this mini-review, we discuss the role of various long non-coding RNAs involved in neurodegenerative disease such as Alzheimer’s and Parkinson’s disease, which can further be studied for the development of potential biomarkers and therapeutic targets for various neurodegenerative diseases.

Neuronal dysfunction and gene modulation by non-coding RNA in Parkinson’s disease and synucleinopathies

“…In recent years, lncRNAs were particularly studied for their role in the regulation of transcription and translation in physiological conditions and disease. Since lncRNA are particularly expressed and conserved in the brain (Ponjavic et al, 2009;Chodroff et al, 2010;Barry, 2014;Yang et al, 2021;Kyzar et al, 2022), their role was investigated in the epigenetic adaption of gene expression in drug addiction, aging, neuroinflammation, brain injury, neurodegenerative and neurodevelopmental diseases (Wang et al, 2018;Srivastava et al, 2021;Sivagurunathan et al, 2022;Yang K. et al, 2022;Mazzeo et al, 2023;Ruffo et al, 2023;Sherazi et al, 2023). The expression rate of lncRNAs is epigenetically modulated.…”

The Role of Tau Pathology in Alzheimer’s Disease and Down Syndrome

“…A recent meta-analysis combining genome-wide association studies (GWAS) expanded the number of AD-risk loci, but most disease-associated variants reside in non-protein coding regions of the genome, such as in long non-coding (lnc) RNAs [ 58 ]. LncRNAs contribute to the pathogenesis of AD via modulating amyloid production, Tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, synaptic impairment and neuroinflammation, and have been thoroughly reviewed previously [ 59 , 60 , 61 , 62 ]. With lncRNA, several therapeutic approaches have been built around competing with endogenous RNA modulation [ 63 ], and determining whether or not various modulation technologies will be effective in physiological contexts remains a high-priority research agenda.…”

Long non-coding RNAs: emerging functional players in the pathobiology and progression of myeloid leukemia

“…From the documented functional roles of this enormous repertoire of lncRNAs, it can be concluded that they regulate gene expression and the epigenetic environment to guide highly precise and complex biological processes; their importance is so far-reaching that it has been considerably underestimated. Regarding the importance of lncRNAs in various biological functions, it is not surprising that they are expressed differentially under various diseases and pathological conditions, such as diabetes, coronary artery disease, neuropsychiatric and neurodegenerative diseases (like schizophrenia and Alzheimer's), and most notably cancers (Wapinski and Chang, 2011;Mitra et al, 2012;Iyer et al, 2015b;Fatima et al, 2015;Lorenzen and Thum, 2016;Schmitz et al, 2016;Lan et al, 2022;Sivagurunathan et al, 2022). The newly released updated Lnc2Cancer3.0 database contains more data on the associations of lncRNAs with cancers (Gao et al, 2021b); there are 9,254 lncRNA-cancer associations, with 2,659 lncRNAs and their associations with 216 human cancer subtypes.…”