Topics

The BACE1-Specific DNA Aptamer A1 Rescues Amyloid-β Pathology and Behavioral Deficits in a Mouse Model of Alzheimer's Disease.

08:00 EDT 12th September 2019 | BioPortfolio

Summary of "The BACE1-Specific DNA Aptamer A1 Rescues Amyloid-β Pathology and Behavioral Deficits in a Mouse Model of Alzheimer's Disease."

Amyloid-β (Aβ) plaque deposits in the brain are considered to be one of the main pathological markers of Alzheimer's disease (AD). The sequential proteolytic cleavage of amyloid precursor protein (APP) by the aspartyl proteases β-site APP-cleaving enzyme 1 (BACE1) and γ-secretase produces Aβ. Therefore, BACE1 inhibition is a very attractive target for the treatment of AD. Our previous work identified a DNA aptamer named A1 that can bind to BACE1 with high affinity and specificity and exhibits a distinct inhibitory effect on BACE1 activity in an AD cell model. The purpose of this research was to test the effect of aptamer A1 in Tg6799 mice. Four-month-old Tg6799 mice were randomly divided into two groups and treated with aptamer A1 and ineffective aptamer A1scr, respectively, by intracerebroventricular injection. Subsequent behavioral experiments showed that treatment with the aptamer A1 improved the cognitive abilities of the AD mice. Western blot indicated that BACE1 and soluble amyloid precursor protein β (sAPPβ) expression significantly decreased in the A1-treated mice. Moreover, aptamer A1 reduced the content of Aβ and the number and density of senile plaques in AD mice. Therefore, our results indicate that aptamer A1 is a novel specific and potent BACE1 inhibitor and is a promising potential target for the treatment of AD.

Affiliation

Journal Details

This article was published in the following journal.

Name: Nucleic acid therapeutics
ISSN: 2159-3345
Pages:

Links

DeepDyve research library

PubMed Articles [13905 Associated PubMed Articles listed on BioPortfolio]

DNA Aptamers Targeting BACE1 Reduce Amyloid Levels and Rescue Neuronal Deficiency in Cultured Cells.

β-amyloid (Aβ) plays an essential role in the pathogenesis of Alzheimer's disease (AD). Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is indispensable for Aβ production, and knockou...

Identification of a BACE1 Binding Peptide Candidate for the Prevention of Amyloid Beta in Alzheimer's Disease.

Amyloid plaques, generated during the progression of Alzheimer's disease, cause major neurological deficits due to substantial cell toxicity and death. The underlying cause of plaque generation stems ...

BACE1-AS prevents BACE1 mRNA degradation through the sequestration of BACE1-targeting miRNAs.

Abnormal long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) participate in the pathophysiology of Alzheimer's disease (AD). However, it remains unclear whether these two types of noncoding RNAs func...

Exosomal DNA Aptamer Targeting α-Synuclein Aggregates Reduced Neuropathological Deficits in a Mouse Parkinson's Disease Model.

The α-synuclein aggregates are the main component of Lewy bodies in Parkinson's disease (PD) brain, and they showed immunotherapy could be employed to alleviate α-synuclein aggregate pathology in PD...

Influence of functional moiety in lupane-type triterpenoids in BACE1 inhibition.

Lupane-type triterpenoids have shown a potential effect against neurodegenerative disorders. Alzheimer's disease, one of the common neurodegenerative disease, is evident by the accumulation of amyloid...

Clinical Trials [6301 Associated Clinical Trials listed on BioPortfolio]

Alzheimer's PET Imaging in Racially/Ethnically Diverse Adults

The study employs tau positron emission tomography (PET) imaging in a well-characterized multi-racial/ethnic cohort to examine the extent to which tau pathology is associated with cognitio...

Effect of Low Dose Radiotherapy on Brain Amyloidosis in the Treatment of Alzheimer's Disease

Alzheimer's Disease (AD) is the most frequent neurodegenerative disease associated with dementia, with a constantly increasing prevalence associated with an aging population. Amyloid depos...

Phase III Study of the Correlation Between Florbetapir F18 PET Imaging and Amyloid Pathology in the Brain

The study is designed to test the relationship between measurements of brain amyloid using florbetapir F 18 PET imaging and true levels of amyloid burden assessed by histology at autopsy. ...

Application of Amyloid PET in Cerebral Amyloid Angiopathy

In this project, we will try to enhance the diagnostic potentials of amyloid PET in CAA by combination of dynamic amyloid PET with MRI SWI and MR perfusion images. We will also try to inve...

Movement Error-processes and Sensorimotor Adaptation in Parkinsonian Patient

The aim of the present project is to document the relationship between the behavioral deficits and the electrophysiological anomalies observed in PD patients in tasks involving motor adapt...

Medical and Biotech [MESH] Definitions

Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.

A type of extracellularly deposited substance composed of an amyloid protein and additional components including HEPARAN SULFATE PROTEOGLYCAN; LAMININ; COLLAGEN TYPE IV; SERUM AMYLOID P-COMPONENT; and APOLIPOPROTEINS E which together form characteristic amyloid fibrils. The core of amyloid fibrils is formed by the stacking of overlapping beta-pleated sheet domains of the amyloid protein. There are many different amyloid proteins that have been found forming the core of the fibrils in vivo. However, amyloid can be formed from any protein that exposes beta-pleated strand conformations during unfolding or refolding. A common characteristic of amyloid is the ability to bind such dyes as CONGO RED and thioflavine.

Proteins that form the core of amyloid fibrils. For example, the core of amyloid A is formed from amyloid A protein, also known as serum amyloid A protein or SAA protein.

Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.

A pancreatic beta-cell hormone that is co-secreted with INSULIN. It displays an anorectic effect on nutrient metabolism by inhibiting gastric acid secretion, gastric emptying and postprandial GLUCAGON secretion. Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS.

Quick Search


DeepDyve research library

Relevant Topics

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Alzheimer's Disease
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...


Searches Linking to this Article