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.
- Rawlings AL, Shadduck PP, Sillin LF, Crookes PF, MacFadyen BV Jr, McDonald MP, Forde KA, Mellinger JD. Professionalism of surgery. Surg Endosc. 2015 Aug;29(8):2072-6. doi: 10.1007/s00464-015-4316-5. Epub 2015 Jul 3. PubMed PMID: 26139484.
- Tan XL, Xue YQ, Ma T, Wang X, Li JJ, Lan L, Malik KU, McDonald MP, Dopico AM, Liao FF. Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment. Mol Neurodegener. 2015 Jun 24;10(1):24. doi: 10.1186/s13024-015-0020-0. PubMed PMID: 26104027; PubMed Central PMCID: PMC4479241.
- Si J, Volkán-Kacsó S, Eltom A, Morozov Y, McDonald MP, Kuno M, Jankó B. Heterogeneous Fluorescence Intermittency in Single Layer Reduced Graphene Oxide. Nano Lett. 2015 Jul 8;15(7):4317-21. doi: 10.1021/acs.nanolett.5b00191. Epub 2015 Jun 19. PubMed PMID: 26057349.
- Rao SK, Ross JM, Harrison FE, Bernardo A, Reiserer RS, Reiserer RS, Mobley JA, McDonald MP. Differential proteomic and behavioral effects of long-term voluntary exercise in wild-type and APP-overexpressing transgenics. Neurobiol Dis. 2015 Jun;78:45-55. doi: 10.1016/j.nbd.2015.03.018. Epub 2015 Mar 25. PubMed PMID: 25818006; PubMed Central PMCID: PMC4426078.
- Maiti P, Manna J, McDonald MP. Merging advanced technologies with classical methods to uncover dendritic spine dynamics: A hot spot of synaptic plasticity. Neurosci Res. 2015 Jul;96:1-13. doi: 10.1016/j.neures.2015.02.007. Epub 2015 Feb 27. Review. PubMed PMID: 25728560.
- 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.