Co-administration of Nanowired DL-3-n-Butylphthalide (DL-NBP) Together with Mesenchymal Stem Cells, Monoclonal Antibodies to Alpha Synuclein and TDP-43 (TAR DNA-Binding Protein 43) Enhance Superior Neuroprotection in Parkinson's Disease Following Concussive Head Injury

Abstract

dl-3-n-butylphthalide (dl-NBP) is one of the potent antioxidant compounds that induces profound neuroprotection in stroke and traumatic brain injury. Our previous studies show that dl-NBP reduces brain pathology in Parkinson's disease (PD) following its nanowired delivery together with mesenchymal stem cells (MSCs) exacerbated by concussive head injury (CHI). CHI alone elevates alpha synuclein (ASNC) in brain or cerebrospinal fluid (CSF) associated with elevated TAR DNA-binding protein 43 (TDP-43). TDP-43 protein is also responsible for the pathologies of PD. Thus, it is likely that exacerbation of brain pathology in PD following brain injury may be thwarted using nanowired delivery of monoclonal antibodies (mAb) to ASNC and/or TDP-43. In this review, the co-administration of dl-NBP with MSCs and mAb to ASNC and/or TDP-43 using nanowired delivery in PD and CHI-induced brain pathology is discussed based on our own investigations. Our observations show that co-administration of TiO₂ nanowired dl-NBP with MSCs and mAb to ASNC with TDP-43 induced superior neuroprotection in CHI induced exacerbation of brain pathology in PD, not reported earlier.

Keywords: Alpha synuclein; Brain pathology; Dopamine; Mesenchymal stem cells; Nanowired delivery; Neuroprotection; Parkinson’s disease; Phosphorylated tau; TDP-43.