Integration of miRNA's theranostic potential with nanotechnology: Promises and challenges for Parkinson's disease therapeutics. (April 2023)

• Record Type: Journal Article
• Authors: Tryphena, Kamatham Pushpa; Singh, Gurpreet; Jain, Naitik; Famta, Paras; Srivastava, Saurabh; Singh, Shashi Bala; Khatri, Dharmendra Kumar
• Is Part Of: Mechanisms of ageing and development. Volume 211(2023)
• Publication Date: 2023-04
• Subjects: PD Parkinson disease -- UTR untranslated region -- SNpc; Substantia nigra pars compacta -- CNS Central nervous system -- ER Endoplasmic reticulum -- UPP Ubiquitin proteasomal pathway -- ALP autophagy lysosomal pathway -- CMA Chaperone mediated autophagy -- LAMP2A Lysosomal associated membrane protein 2 -- Hsp Heat shock protein -- PUMA Proteins like p53 upregulated modulator of apoptosis -- Psmd3 Proteasome 26 S subunit, non-ATPase 3 -- UPR Unfolded protein response -- PRKN Parkin RBR E3 Ubiquitin Protein Ligase -- LRRK2 Leucine-rich repeat kinase 2 -- PINK1 PTEN Induced Kinase 1 -- VDAC-1 Voltage-dependent anion-selective channel -- PGC-α Peroxisome proliferator-activated receptor-gamma coactivator -- DRP1 dynamin-related protein 1 -- NLRP3 NLR family pyrin domain containing 3 -- GSK-3β Glycogen synthase kinase 3 -- GLRX glutathione-protein mixed disulfides -- PitX3 Pituitary homeobox 3 -- Nrf2 nuclear factor erythroid 2–related factor 2 -- Keap1 Kelch-like ECH-associated protein 1 -- IGF-1 insulin-like growth factor 1 -- AXIN1 Axis inhibition protein -- Nurr1 Nuclear receptor related 1 -- DAPK1 Death-associated protein kinase -- PTEN Phosphatase and TENsin homolog deleted on chromosome 10 -- MAPK mitogen-activated protein kinases -- JNK Jun N-terminal kinases -- RIPK RIPK1-like protein receptor-interacting protein kinase -- BECN1 Beclin1 -- DRP-1 Dynamin related protein -- 6-OHDA 6-hydroxydopamine -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- SIRT1 Sirtuin1 -- NPs Nanoparticles -- BBB Blood brain barrier -- RVG Rabies virus glycoprotein -- AUC AArea under curve -- FC Fold change; Parkinson's disease -- MicroRNA -- Biomarkers -- Agomir -- Antagomir -- Nanoparticles; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2023.111800
• Languages: English
• ISSNs: 0047-6374

Abstract

Abstract: Despite the wide research going on in Parkinson's disease (PD), the burden of PD still remains high and continues to increase. The current drugs available for the treatment of PD are only aimed at symptomatic control. Hence, research is mainly focused on identifying the novel therapeutic targets that can be effectively targeted in order to slow down or culminate the disease progression. Recently the role of microRNAs (miRNAs) in the regulation of various pathological mechanisms of PD has been thoroughly explored and many of them were found to be dysregulated in the biological samples of PD patients. These miRNAs can be used as diagnostic markers and novel therapeutic options to manage PD. The delivery of miRNAs to the target site in brain is a challenging job owing to their nature of degradability by endonucleases as well as poor blood brain barrier (BBB) permeability. Nanoparticles appear to be the best solution to effectively encase the miRNA in their core as well as cross the BBB to deliver them into brain. Functionalisation of these nanoparticles further enhances the site-specific delivery. Graphical Abstract: ga1 Highlights: miRNAs are involved in the regulation of various mechanisms implicated in the pathogenesis of Parkinson's disease (PD). Many miRNAs are found to be dysregulated in PD. Circulatory miRNAs can be used as biomarkers in PD. miRNA mimics and inhibitors could be potential therapeutic options to manage PD. Nanotechnology offers a solution for the challenges related to miRNA delivery. Nanoparticles can be used as carriers to deliver miRNA to target sites in the brain.