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Researchers
  • Dr.  Ronit Sharon
Dr Ronit Sharon
 
Research Interests
The laboratory is focusing on biochemical, molecular and cell biology aspects of neuronal degeneration during aging of the mammalian brain. Particularly, Parkinson’s diseases (PD) and the related synucleinopathies, and Alzheimer’s disease.
 
We perform extensive studies of the trafficking and processing of alpha synuclein (a-Syn), a protein critically implicated in the pathogenesis of PD and the synucleinopathies. We have discovered that a-Syn normally interacts with brain lipids and affects their content in neurons.  We have further shown that a-Syn associations with brain lipids play an important role in the pathogenic mechanism progressively leading to its missfolding, aggregation and accumulation in Lewy bodies, the prototype pathogenic insults.
 
Interested to elucidate the normal function of the a-Syn protein in the healthy brain, we found that a-Syn  protein normally act to activate mechanisms of synaptic vesicle recycling following neuronal stimulations, a process that affects among other effects, mechanisms of learning and memory. The function of a-Syn and the toxic properties of its various assemblies is tested in cultured neurons and in relevant mouse models.
 
 
Lab Members
Jessica Grigoletto
Suaad Abedelhadi
​Jessica Grigoletto
Suaad Abedelhadi
JessicaG@ekmd.huji.ac.il suaada@ekmd.huji.ac.il
Dana Komisarov
​Meir Shechter
Dana Komisarov
​Meir Shechter
danako@ekmd.huji.ac.il meir.schechter@mail.huji.ac.il
  

Publications

1. Sharon R, Goldberg MS, Bar-Josef I, Betensky RA, Shen J, Selkoe DJ. alpha-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins. Proc Natl Acad Sci U S A 2001b; 98: 9110-5.

2. Sharon R, Bar-Joseph I, Frosch MP, Walsh DM, Hamilton JA, Selkoe DJ. The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson’s disease. Neuron 2003a; 37: 583-95.

3. Sharon R, Bar-Joseph I, Mirick GE, Serhan CN, Selkoe DJ. Altered fatty acid composition of dopaminergic neurons expressing alpha-synuclein and human brains with alpha-synucleinopathies. J Biol Chem 2003b; 278: 49874-81.

4. Assayag K, Yakunin E, Loeb V, Selkoe DJ, Sharon R. Polyunsaturated fatty acids induce alpha-synuclein-related pathogenic changes in neuronal cells. Am J Pathol 2007; 171: 2000-11. PMCID: PMC2111122

5.  Haviv Y, Avrahami D, Ovadia H, Ben-Hur T, Gabizon R, Sharon R. Induced neuroprotection independently from PrPSc accumulation in a mouse model for prion disease treated with simvastatin. Arch Neurol 2008; 65: 762-75.

6. Ben Gedalya T, Loeb V, Israeli E, Altschuler Y, Selkoe DJ, Sharon R. Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling. Traffic 2009; 10: 218-34. PMCID: PMC2694501

7. Israeli E, Sharon R. Beta-synuclein occurs in vivo in lipid-associated oligomers and forms hetero-oligomers with alpha-synuclein. J Neurochem 2009; 108: 465-74.

8. Yakunin E, Moser A, Loeb V, Saada A, Faust P, Crane DI, Baes M, Sharon, R. alpha-Synuclein abnormalities in mouse models of peroxisome biogenesis disorders. J Neurosci Res 2009; 88: 866-876.

9. Loeb V, Yakunin E, Saada A, Sharon R. The transgenic over expression of (16)-Synuclein and not its related pathology, associates with complex I inhibition. J Biol Chem 2010, 5;285(10):7334-43.

10. Israeli E, Yakunin e, Zarbiv Y, Hacohen-Solovich A, Kisos H, Loeb V, Lichtenstein M, Ben-Gedalya T, Sabag O, Pikarsky E, Lorberboum-Galski H, Sharon R. α-synuclein expression selectively affects tumorigenesis in mice modeling Parkinson’s disease.PLoS One 2011, 6 (5) e19622

11. Yakunin Y, Loeb V, Kisos H, Biala Y, Yehuda S, Yaari Y, Selkoe D, Sharon R. Docosahexaenoic acid controls α-synuclein neuropathology in a mouse model.  Brain Pathology. 2011, Epub Sep. 20

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