Mice lacking major brain gangliosides develop Parkinsonism

Gusheng Wu, Zi Hua Lu, Neil Kulkarni, Ruchi Amin, Robert W. Ledeen

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Parkinson's disease (PD) is the second most prevalent late-onset neurodegenerative disorder that affects nearly 1% of the global population aged 65 and older. Whereas palliative treatments are in use, the goal of blocking progression of motor and cognitive disability remains unfulfilled. A better understanding of the basic pathophysiological mechanisms underlying PD would help to advance that goal. The present study provides evidence that brain ganglioside abnormality, in particular GM1, may be involved. This is based on use of the genetically altered mice with disrupted gene Galgt1 for GM2/GD2 synthase which depletes GM2/GD2 and all the gangliotetraose gangliosides that constitute the major molecular species of brain. These knockout mice show overt motor disability on aging and clear indications of motor impairment with appropriate testing at an earlier age. This disability was rectified by L-dopa administration. These mice show other characteristic symptoms of PD, including depletion of striatal dopamine (DA), loss of DA neurons of the substantia nigra pars compacta, and aggregation of alpha synuclein. These manifestations of parkinsonism were largely attenuated by administration of LIGA-20, a membrane permeable analog of GM1 that penetrates the blood brain barrier and enters living neurons. These results suggest that perturbation of intracellular mechanisms mediated by intracellular GM1 may be a contributing factor to PD.

Original languageEnglish (US)
Pages (from-to)1706-1714
Number of pages9
JournalNeurochemical Research
Issue number9
StatePublished - Sep 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience


  • Alpha synuclein
  • Dopaminergic neurons
  • GM1 ganglioside
  • LIGA-20
  • Parkinson's disease


Dive into the research topics of 'Mice lacking major brain gangliosides develop Parkinsonism'. Together they form a unique fingerprint.

Cite this