Michael P. McDonald, Ph.D.
Department of Neurology
The University of Tennessee Health Science Center
855 Monroe Avenue, Suite 415
Memphis, TN 38163
Phone: (901) 448-4648
Fax: (901) 448-4685
Office: 422 Wittenborg Anatomy Building
Email: Michael P. McDonald
Our lab studies the involvement of gangliosides in the behavioral and cognitive impairments, protein misfolding, and neurodegeneration of Alzheimer's and Parkinson's diseases. Gangliosides are glycolipids richly expressed in neuronal membranes. Although the functions of gangliosides are not completely understood, converging evidence clearly demonstrates a critical role for membrane gangliosides in the binding and aggregation of amyloid-β (Aβ), the toxic peptide that aggregates into plaques in Alzheimer's disease. Our previous research showed that elimination of the GD3 synthase (GD3S) gene significantly reduces Aβ binding and Aβ -induced cell death in primary neuronal cultures. In a mutant mouse model of Alzheimer's disease, knocking out GD3S nearly eliminates plaque formation and Aβ -associated neuropathology, and reverses memory deficits. Because GD3 ganglioside is a critical mediator of the ceramide-sphingomyelin-mediated apoptotic pathway, we expect that inhibiting GD3S will also be neuroprotective in models of Parkinson's disease. In addition to targeted mutation of GD3S, ongoing experiments involve injection of viral-vector-mediated small-interfering RNA (siRNA) constructs to "silence" GD3S, and intracranial infusion of v. cholerae sialidase (VCS), an enzyme that hydrolyzes specific sialic acid residues on gangliosides. Both of these manipulations have the effect of reducing levels of the more-complex brain gangliosides, which have a high affinity for Aβ, and increasing levels of the less-complex brain gangliosides, which have a lower affinity for Aβ and are neuroprotective. We expect this line of research to provide insight into new therapeutic targets for Alzheimer's and Parkinson's diseases.
- Sokolov DA, Morozov YV, McDonald MP, Vietmeyer F, Hodak JH, Kuno M. Direct observation of single layer graphene oxide reduction through spatially resolved, single sheet absorption/emission microscopy. Nano Lett. 2014 Jun 11;14(6):3172-9. doi: 10.1021/nl500485n. Epub 2014 May 22. PubMed PMID: 24831202.
- Flanigan TJ, Xue Y, Kishan Rao S, Dhanushkodi A, McDonald MP. Abnormal vibrissa-related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics. Genes Brain Behav. 2014 Mar 21. doi: 10.1111/gbb.12133. [Epub ahead of print] PubMed PMID: 24655396; PubMed Central PMCID: PMC4170055.
- Zhukovskyi M, Sanchez-Botero L, McDonald MP, Hinestroza J, Kuno M. Nanowire-functionalized cotton textiles. ACS Appl Mater Interfaces. 2014 Feb 26;6(4):2262-9. doi: 10.1021/am4052602. Epub 2014 Feb 5. PubMed PMID: 24471981.
- McDonald MP, Vietmeyer F, Aleksiuk D, Kuno M. Supercontinuum spatial modulation spectroscopy: detection and noise limitations. Rev Sci Instrum. 2013 Nov;84(11):113104. doi: 10.1063/1.4829656. PubMed PMID: 24289385.
- McDonald MP, Eltom A, Vietmeyer F, Thapa J, Morozov YV, Sokolov DA, Hodak JH, Vinodgopal K, Kamat PV, Kuno M. Direct observation of spatially heterogeneous single-layer graphene oxide reduction kinetics. Nano Lett. 2013;13(12):5777-84. doi: 10.1021/nl402057j. Epub 2013 Nov 21. PubMed PMID: 24245975.
- Ariga T, Itokazu Y, McDonald MP, Hirabayashi Y, Ando S, Yu RK. Brain gangliosides of a transgenic mouse model of Alzheimer's disease with deficiency in GD3-synthase: expression of elevated levels of a cholinergic-specific ganglioside, GT1aÎ±. ASN Neuro. 2013 May 30;5(2):141-8. doi: 10.1042/AN20130006. PubMed PMID: 23565921; PubMed Central PMCID: PMC3667643.