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

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

Publication date: Sep 06, 2019

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. Recently we have generated DNA aptamers that specifically recognize α-synuclein. In this study, we further investigated the in vivo effect of these aptamers on the neuropathological deficits associated with PD. For efficient delivery of the aptamers into the mouse brain, we employed modified exosomes with the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface. We demonstrated that the aptamers were efficiently packaged into the RVG-exosomes and delivered into neurons in vitro and in vivo. Functionally, the aptamer-loaded RVG-exosomes significantly reduced the α-synuclein preformed fibril (PFF)-induced pathological aggregates, and rescued synaptic protein loss and neuronal death. Moreover, intraperitoneal administration of these exosomes into the mice with intra-striatally injected α-synuclein PFF reduced the pathological α-synuclein aggregates and improved motor impairments. In conclusion, we demonstrated that the aptamers targeting α-synuclein aggregates could be effectively delivered into the mouse brain by the RVG-exosomes and reduce the neuropathological and behavioral deficits in the mouse PD model. This study highlights the therapeutic potential of the RVG-exosome delivery of aptamer to alleviate the brain α-synuclein pathology.

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Concepts Keywords
Aptamer Aptamer
Brain Parkinson’s disease
Exosome Exosome
Exosomes Vesicles
Fibril Lewy body dementia
Glycoprotein Medicine
Immunotherapy Branches of biology
Intraperitoneal Administration Specific rabies
Lewy Bodies Immunotherapy
Membrane
Neuron
Neurons
Neuropathological
Nucleic
Parkinson
Pathology
Peptide
Rabies
Synaptic
Viral

Semantics

Type Source Name
pathway BSID Aging
disease MESH Aging
disease DOID tauopathy
disease MESH tauopathy
gene UNIPROT ACTA1
gene UNIPROT SCN8A
gene UNIPROT MBNL1
drug DRUGBANK Morphine
gene UNIPROT COCH
gene UNIPROT TNIP1
gene UNIPROT MLXIP
gene UNIPROT MYLIP
gene UNIPROT MARCH8
drug DRUGBANK Carboxyamidotriazole
disease MESH tumor
pathway BSID Neurodegenerative Diseases
disease MESH neurodegenerative diseases
gene UNIPROT PROC
gene UNIPROT IGFALS
disease DOID ALS
drug DRUGBANK Trehalose
gene UNIPROT MAPT
gene UNIPROT DHDDS
gene UNIPROT CIT
drug DRUGBANK L-Citrulline
gene UNIPROT PELI1
gene UNIPROT GRAP2
gene UNIPROT DDX53
drug DRUGBANK Ethanol
gene UNIPROT CALM1
drug DRUGBANK L-Tyrosine
gene UNIPROT MBOAT4
gene UNIPROT ADCY10
drug DRUGBANK Xylazine
drug DRUGBANK Ketamine
disease MESH suffering
drug DRUGBANK Dimethyl sulfoxide
gene UNIPROT CES2
gene UNIPROT CASP1
gene UNIPROT ERVK-21
gene UNIPROT ERVK-18
gene UNIPROT HERV-K104
gene UNIPROT ERVK-10
gene UNIPROT HERVK_113
gene UNIPROT ERVK-19
gene UNIPROT ERVK-25
gene UNIPROT ERVK-24
gene UNIPROT ERVK-8
gene UNIPROT ERVK-6
gene UNIPROT ERVK-7
gene UNIPROT ERVK-9
drug DRUGBANK Sucrose
drug DRUGBANK L-Glutamine
drug DRUGBANK L-Lysine
gene UNIPROT KIT
drug DRUGBANK Acetate ion
drug DRUGBANK Activated charcoal
drug DRUGBANK Flunarizine
drug DRUGBANK Streptomycin
gene UNIPROT F12
gene UNIPROT ATF7IP
disease DOID neuroblastoma
disease MESH neuroblastoma
gene UNIPROT FBXO8
gene UNIPROT FBRS
drug DRUGBANK Esomeprazole
gene UNIPROT PRDM10
drug DRUGBANK Tromethamine
drug DRUGBANK Aspartame
disease MESH CNS diseases
gene UNIPROT TNFSF14
gene UNIPROT SET
disease MESH diagnosis
gene UNIPROT MARK1
disease MESH relapse
gene UNIPROT ARSA
drug DRUGBANK Acetylsalicylic acid
gene UNIPROT ENDOG
disease MESH development
gene UNIPROT TALDO1
gene UNIPROT LRSAM1
gene UNIPROT AIF1
drug DRUGBANK Acetylcholine
gene UNIPROT WIPF2
gene UNIPROT GFAP
gene UNIPROT IK
gene UNIPROT MENT
drug DRUGBANK Trestolone
gene UNIPROT SLC26A5
gene UNIPROT SNAP25
gene UNIPROT MAP2
gene UNIPROT OCA2
drug DRUGBANK Proline
disease MESH ***p
gene UNIPROT NR1H4
gene UNIPROT BFAR
gene UNIPROT PDCD6IP
gene UNIPROT SYNM
gene UNIPROT SLC35G1
gene UNIPROT DESI1
gene UNIPROT NOVA2
gene UNIPROT TNMD
drug DRUGBANK Tretamine
drug DRUGBANK Sodium lauryl sulfate
gene UNIPROT SDS
disease MESH separated
drug DRUGBANK Lysozyme
gene UNIPROT LARGE1
gene UNIPROT GKN2
gene UNIPROT DEPP1
gene UNIPROT GOPC
disease DOID synucleinopathies
gene UNIPROT TRA
gene UNIPROT KCNK3
gene UNIPROT ACOT11
gene UNIPROT RNH1
gene UNIPROT MAL
gene UNIPROT MRTFA
gene UNIPROT TIRAP
gene UNIPROT CD8A
drug DRUGBANK Aducanumab
disease DOID PDD
disease DOID dementia
disease MESH dementia
gene UNIPROT NFKBIZ
disease MESH Brain Disorders
disease MESH death
disease DOID rabies
disease MESH rabies

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