Current Research Interests/Projects:

(a) Ganglioside function in the neuron.
Gangliosides have long been known to be major glycoconjugates of neuronal membranes, but their functional role(s) has remained obscure. Our research has focused on the mechanisms by which they regulate calcium flux across membranes; this includes the nuclear- as well as the plasma membrane. Their developmental appearance in the former coincides with axonal outgrowth and serves a neuroprotective function. This study is designed to help elucidate the reason that gangliosides are proving useful as therapeutic agents in the treatment of Parkinson's disease.

(b) Myelin metabolic activity and demyelination.
Our lab and others have shown myelin to contain many enzymes that synthesize myelin lipids. We are currently studying aspartoacylase, an enzyme of myelin that cleaves the acetyl group from N-acetylaspartate, thereby providing substrate for myelin lipid synthesis. We also study the presence of cytokine receptors in myelin that may have a role in demyelination in such conditions as multiple sclerosis.

Representative Publications:

Wu G, Lu Z-H, and Ledeen RW (1995) Induced and spontaneous neuritogenesis are associated with enhanced expression of ganglioside GM1 in the nuclear membrane. J. Neurosci. 15: 3739-3746.

Wu G, Lu Z-H, and Ledeen RW (1995) GM1 ganglioside in the nuclear membrane modulates nuclear calcium homeostasis during neurite outgrowth. J. Neurochem. 65: 1419-1422.

Chakraborty G, Ziemba S, Drivas A, and Ledeen RW (1997) Myelin contains neutral sphingomyelinase activity that is stimulated by TNF- . J. Neurosci. Res. 50: 466-476.

Kozireski-Chuback D, Wu G, and Ledeen RW (1999) Upregulation of nuclear GM1 accompanies axon-like, but not dendrite-like, outgrowth in NG108-15 cells. J. Neurosci. Res. 55: 107-118.

Chakraborty G, Drivas A, and Ledeen RW (1999) The phosphoinositide signaling cycle in myelin requires cooperative interaction with the axon. Neurochem. Res. 24: 249-254.

Chakraborty G, Mekala P, Yahya D, Wu G, and Ledeen RW (2001) Intraneuronal N-acetylaspartate supplies acetyl groups for myelin synthesis: evidence for myelin-associated aspartoacylase. J. Neurochem. 78: 736-745.

Wu G, Xie X, Lu Z-H, and Ledeen RW (2001) Cerebellar neurons lacking complex gangliosides degenerate in the presence of depolarizing levels of potassium. Proc. Natl. Acad. Sci. 98: 307-312.

Xie X, Wu G, Lu Z-H, and Ledeen RW (2002) Potentiation of a sodium-calcium exchanger in the nuclear envelope by nuclear GM1 ganglioside. J. Neurochem. 81: 1185-1195.

Ledeen RW and Wu G (2002 Ganglioside function in calcium homeostasis and signaling. Neurochem. Res. 27:637-647.

Xie X, Wu G, and Ledeen RW (2004) C6 cells express a sodium-calcium exchanger/GM1 complex in the nuclear envelope but have no exchanger in the plasma membrane: comparison to astrocytes. J. Neurosci. Res. 76:363-375.

Ledeen RW and Wu G (2004) Nuclear lipids: key signaling effectors in the nervous system and other tissues. J. Lipid Res. 45:1-8.