LncRNA MALAT1 potentiates inflammation disorder in Parkinson's disease

Abstract

Parkinson's disease (PD), a chronic neurodegenerative disease that primarily affects middle-aged and elderly people (Tang et al., 2017) is pathologically featured by programmed death of dopaminergic neurons and accumulation of α-synuclein (α-syn)-based Lewy body (Hirsch et al., 2016). According to epidemiological surveys, global prevalence of PD is estimated to surpass 14 million by 2040 (Dorsey & Bloem, 2018), and over a half of them are likely to deteriorate into dementia (Global Parkinson's Disease Survey Steering, 2002), which renders patients dysfunctional in non-motor and motor aspects, including anxiety, olfactory dysfunction, memory disorder, resting tremor, muscle stiffness, postural instability and bradykinesia (Devos et al., 2013; Rial et al., 2014). To make matters worse, management of PD remains undesirable, so clarification of PD aetiology is of paramount importance.Chronic inflammation is a pathological trait shared by plenty of neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis and PD (Figueiredo-Pereira et al., 2014;Russo et al., 2014). It has been documented that long noncoding RNAs (lncRNAs), such as LincRNA-Cox2, lncRNA THRIL and lncRNA NEAT1, are broadly involved in regulating inflammation responses of monocytes, macrophages and other immune cells (Heward & Lindsay, 2014). Taking lncRNA MALAT1 for instance, its interaction with serum amyloid A3 (SAA3) prompted high glucose-exposed endothelial cells to secrete inflammatory factors (e.g. TNFα and IL-6) (Puthanveetil et al., 2015), and its knockout restrained excessive inflammation in LPS-induced septic mice models by up-regulating miR-146a

Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase

“…The identity of the neurotoxin that triggers the degenerative process of the neuromelanin-containing dopaminergic neurons of the nigrostriatal system is unclear. However, there is general agreement in the scientific community that this degenerative process involves oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, neuroinflammation, dysfunction of protein degradation of the lysosomal and proteasomal systems, and aggregation of alpha-synuclein to neurotoxic oligomers [ 33 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. However, what triggers these neurotoxic mechanisms in idiopathic Parkinson’s disease is still unknown.…”

Morinda officinalis extract exhibits protective effects against atopic dermatitis by regulating the MALAT1/miR‐590‐5p/CCR7 axis

“…Increasing evidence has been reported that lncRNAs play a crucial role in many biological functions and disease processes 37 . LncRNA MALAT1, as an important lncRNA, is usually aberrantly expressed in varieties of human disease, such as osteoarthritis, 38 diabetic retinopathy, 39 human cancers, 40 neuropathic pain, 41 and parkinson's disease 42 . For instance, the expression of MALAT1 is notably elevated in osteoarthritis, this upregulation augments chondrocytes cell proliferation, apoptosis, and ECM degradation, 38 and another research reported that MALAT1 act as a regulator of inflammation in diabetic, the MALAT1 level is enhanced in the vitreous humors 39 .…”

Roles of long noncoding RNAs in human inflammatory diseases

“… lncRNA Expression level Samples Localization Factors Molecular mechanism Reference SNHG7 upregulation serum of PD patients cytoplasm IL-1β, IL-6, and TNF-α regulating miR-425-5p/TRAF5 axis [ 71 ] HOTAIR upregulation APP/PS1 mice cytoplasm IL-1β, IL-6, and TNF-α sponging miR-130a-3p [ 72 ] MALAT1 upregulation serum of PD patients not mentioned IL-1β, IL-6, and TNF-α sponging miR155, miR124, or targeting NF-κB? [ 73 ] TUG1 upregulation serum of PD patients not mentioned IL-1β, IL-6, and TNF-α not mentioned [ 76 ] …”

“…Uncertain regulatory mechanisms MALAT1 and TUG1 lncRNAs were upregulated in the serum of PD patients. MALAT1 could increase the secretion of IL-1β, IL-6, and TNF-α in LPS-treated PC12 cells and induce an inflammatory response [73]. The underlying mechanism may involve sponging miR155, miR124, or targeting NF-κB; however, more convincing evidence is required [74,75].…”