Nanocarriers to mediate the pathways from diabetes toward Parkinson's disease

Background: The connection between type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD) was first pointed out in the early 1960s. This probable link is still under serious consideration nowadays. Methods: Neurological changes caused by T2DM could be relevant to PD that included neuroinflammation, dopaminergic deregulation, reduction in the expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha, increment in the expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes 15 and acceleration of alpha-synuclein (alpha-Syn) amyloid fibril formation. Furthermore, medical evidence disclosed that significantly exacerbated PD symptoms were associated with the initiation of T2DM, and common genes were concurrently found in DNA of T2DM and PD patients. Insulin resistance and microbiota dysbiosis of the gut-brain axis also connected DM to PD, explaining DM could be a risk factor for PD. In terms of treatment, antidiabetic drugs appeared to engender a certain degree of neuroprotective activity against PD. During drug delivery to the central nervous system, biomaterials could play a crucial role in permeating the blood-brain barrier (BBB) and recognizing exact cerebral tissue to rescue neurons from degeneration. Exosomes, liposomes, micelles, solid lipid nanoparticles, dendrimers, niosomes and nano-sized polymers have been developed to enhance drug and gene efficacy in brain targeting for PD management. In order to boost BBB permeability and alpha-Syn conjugation, the surface of these nanocarriers (NCs) were modified with active biomolecules, for instance, lactoferrin, angiopep and OX26. Natural exosomes were exposed to a limited number, and can be an efficient vector in analyzing the pathways from DM toward PD for clinical trials. Significant findings: This review focuses on understanding the pathophysiological relation between T2DM and PD, and the treatment for the two diseases with NCs. We also highlight the problems that have been solved and the challenges that continue.