The emerging role of non-coding RNAs from extracellular vesicles in Alzheimer’s disease

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.

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Inflamma-MicroRNAs in Alzheimer’s Disease: From Disease Pathogenesis to Therapeutic Potentials

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.785433 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yuanyuan Liang ◽

Lin Wang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Messenger Rna ◽

Senile Dementia ◽

Therapeutic Targets ◽

Peripheral Circulation ◽

Diagnostic Biomarkers ◽

Non Coding Rnas ◽

Shed Light

Alzheimer’s disease (AD) is the most common cause of senile dementia. Although AD research has made important breakthroughs, the pathogenesis of this disease remains unclear, and specific AD diagnostic biomarkers and therapeutic strategies are still lacking. Recent studies have demonstrated that neuroinflammation is involved in AD pathogenesis and is closely related to other health effects. MicroRNAs (miRNAs) are a class of endogenous short sequence non-coding RNAs that indirectly inhibit translation or directly degrade messenger RNA (mRNA) by specifically binding to its 3′ untranslated region (UTR). Several broadly expressed miRNAs including miR-21, miR-146a, and miR-155, have now been shown to regulate microglia/astrocytes activation. Other miRNAs, including miR-126 and miR-132, show a progressive link to the neuroinflammatory signaling. Therefore, further studies on these inflamma-miRNAs may shed light on the pathological mechanisms of AD. The differential expression of inflamma-miRNAs (such as miR-29a, miR-125b, and miR-126-5p) in the peripheral circulation may respond to AD progression, similar to inflammation, and therefore may become potential diagnostic biomarkers for AD. Moreover, inflamma-miRNAs could also be promising therapeutic targets for AD treatment. This review provides insights into the role of inflamma-miRNAs in AD, as well as an overview of general inflamma-miRNA biology, their implications in pathophysiology, and their potential roles as biomarkers and therapeutic targets.

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Long Non-coding RNA: Insight Into Mechanisms of Alzheimer's Disease

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.821002 ◽

2022 ◽

Vol 14 ◽

Author(s):

Zhen Lan ◽

Yanting Chen ◽

Jiali Jin ◽

Yun Xu ◽

Xiaolei Zhu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Vital Role ◽

Biological Functions ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna ◽

Insight Into

Alzheimer's disease (AD), a heterogeneous neurodegenerative disorder, is the most common cause of dementia accounting for an estimated 60–80% of cases. The pathogenesis of AD remains unclear, and no curative treatment is available so far. Increasing evidence has revealed a vital role of non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), in AD. LncRNAs contribute to the pathogenesis of AD via modulating amyloid production, Tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, synaptic impairment and neuroinflammation. This review describes the biological functions and mechanisms of lncRNAs in AD, indicating that lncRNAs may provide potential therapeutic targets for the diagnosis and treatment of AD.

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Recent advances on the role of long non-coding RNAs in Alzheimer's disease

Neural Regeneration Research ◽

10.4103/1673-5374.284990 ◽

2020 ◽

Vol 15 (12) ◽

pp. 2253 ◽

Cited By ~ 2

Author(s):

ManishK Tripathi ◽

MohammadMoshahid Khan ◽

Kyle Doxtater

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Recent Advances ◽

Non Coding Rnas

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CHAPTER 7. The Role of Extracellular Vesicles in the Neuronal System: Application of Extracellular Vesicles in Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis, and Dementia

10.1039/9781839164552-00161 ◽

2021 ◽

pp. 161-189

Author(s):

K. Groen

Keyword(s):

Multiple Sclerosis ◽

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Extracellular Vesicles ◽

System Application ◽

Neuronal System

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Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer’s disease

Molecular Neurodegeneration ◽

10.1186/s13024-017-0191-y ◽

2017 ◽

Vol 12 (1) ◽

Cited By ~ 26

Author(s):

Ellis Patrick ◽

Sathyapriya Rajagopal ◽

Hon-Kit Andus Wong ◽

Cristin McCabe ◽

Jishu Xu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Non Coding Rnas

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Advances with Long Non-Coding RNAs in Alzheimer’s Disease as Peripheral Biomarker

Genes ◽

10.3390/genes12081124 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1124

Author(s):

Maria Garofalo ◽

Cecilia Pandini ◽

Daisy Sproviero ◽

Orietta Pansarasa ◽

Cristina Cereda ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Significant Role ◽

Rna Processing ◽

Diagnostic Biomarkers ◽

Non Coding Rnas ◽

Peripheral Biomarker

One of the most compelling needs in the study of Alzheimer’s disease (AD) is the characterization of cognitive decline peripheral biomarkers. In this context, the theme of altered RNA processing has emerged as a contributing factor to AD. In particular, the significant role of long non-coding RNAs (lncRNAs) associated to AD is opening new perspectives in AD research. This class of RNAs may offer numerous starting points for new investigations about pathogenic mechanisms and, in particular, about peripheral biomarkers. Indeed, altered lncRNA signatures are emerging as potential diagnostic biomarkers. In this review, we have collected and fully explored all the presented data about lncRNAs and AD in the peripheral system to offer an overview about this class of non-coding RNAs and their possible role in AD.

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Role of Extracellular vesicles in Alzheimer’s disease: Current Advances

Current Molecular Medicine ◽

10.2174/1566524021666210406121807 ◽

2021 ◽

Vol 21 ◽

Author(s):

Smriti Sharma

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Extracellular Vesicles ◽

Neurodegenerative Disorder ◽

Future Research ◽

Brain Pathology ◽

Recent Developments ◽

Available Information ◽

Potential Use

: The recent developments in the field of extracellular vesicles (EVs) point to their potential use for predicting and treating neurodegenerative diseases. This reviews focusses on the importance and latest advances in this field especially with respect to Alzheimer’s disease (AD). Increasing evidence show that progression of amyloid-beta and tau brain pathology is correlated to the cognitive decline associated with AD. Lot of experimental data suggests involvement of EVs with these processes for instance EVs are known to circulate the misfolded proteins involved in AD. The currently available information on role of EVs in neurodegenerative disorder especially in AD and have also presented the knowledge gaps on which future research efforts should be focused.The recent developments in the field of extracellular vesicles (EVs) point to their potential use for predicting and treating neurodegenerative diseases. This reviews focusses on the importance and latest advances in this field especially with respect to Alzheimer’s disease (AD). Increasing evidence show that progression of amyloid-beta and tau brain pathology is correlated to the cognitive decline associated with AD. Lot of experimental data suggests involvement of EVs with these processes for instance EVs are known to circulate the misfolded proteins involved in AD. The currently available information on role of EVs in neurodegenerative disorder especially in AD and have also presented the knowledge gaps on which future research efforts should be focused.

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