Recuperative effect of metformin loaded Polydopamine Nanoformulation promoting EZH2 mediated proteasomal degradation of phospho-α-Synuclein in Parkinson's disease model

Publication date: Available online 31 August 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Mo. Nadim Sardoiwala, Anup K. Srivastava, Babita Kaundal, Surajit Karmakar, Subhasree Roy ChoudhuryAbstractPosttranslational modification and agglomeration of α-Synuclein (α-Syn), mitochondrial dysfunction, oxidative stress and loss of dopaminergic neurons are hallmark of Parkinson's disease (PD). This paper evaluates neuroprotection efficacy of nature inspired bio-compatible polydopamine nanocarrier for metformin delivery (Met encapsulated PDANPs) by crossing blood brain barrier in in vitro, 3D and in vivo experimental PD models. The neuroprotective potential was arbitrated by downregulation of phospho-serine 129 (pSer129) α-Syn, with reduction in oxidative stress, prevention of apoptosis and anti-inflammatory activities. The neuroprotective mechanism proved novel interaction of epigenetic regulator EZH2 mediated ubiquitination and proteasomal degradation of aggregated pSer129 α-Syn. In summary, this study divulges the neuroprotective role of Met loaded PDANPs by reversing the neurochemical deficits by confirming an epigenetic mediated nanotherapeutic approach for the PD prevention.Graphical AbstractMetformin nanoformulation [Metformin loaded Polydopamine nanoparticles] being synthesized by solution oxidation mediated self-assembly of dopamine molecules. Rotenone exposure inhibit ETC complex I of SH-SY5Y cells, thus depletion of ATP leads to simulate PD e...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research