Silke Nuber

Silke Nuber

Assistant Professor of Neurology
Silke Nuber
The Nuber lab is dedicated to studying one of the top-most genetic risk factors for Parkinson’s disease (PD) -- α-synuclein -- in unique PDlike

Characterization and behavioral consequences of human α-synuclein in mouse brain.

We use mice expressing the human wildtype or mutant α-synuclein and its amplifications (i.e. triplication) under the control of neuronal
promoters, and these recapitulate human α-synucleinopathies down to the ultrastructural level. Motor behavior of the familial PD-E46K
amplified 3K α-synuclein mice is impaired at 3 months and fully developed at 6 months. The striking PD-like phenotypes are based on
shifting of α-synuclein tetramers toward excess monomers, that cluster with vesicles, and these develop more mildly in our lower
expressing ‘3KL’ and familial PD (E46K, G51D) mice. We aim to understand the earliest changes and mechanisms occurring by 3K
when compared to bone fide PD mutations. We analyze the motor & cognitive phenotypes and underlying brain pathologies.

Endocrine conditions in PD.

Our major research endeavor is to investigate endocrine neuroprotection in PD-like mice since we found benefit of female sex, similar
to human PD. We use estrogen and estrogen receptor modulators to study its impact on α-synuclein biology.

Regulation and neuronal effects of lipids modulators.

The lipid desaturase SCD is a key enzyme associating with α-synuclein assembly and toxicity in cell culture. We investigate the impact
of SCD on α-synuclein pathophysiology by changing the lipid saturation state using genetic crossings and pharmacological inhibition in

Lysosomal anomalities and GBA activity.

Deficiency in GBA, a lysosomal lipid-modulator, is the major PD risk-factor and impacts the α-synuclein tetramer:monomer ratio in PDderived
neurons. In PD brain, lysosomal vesicle aggregates are observed, and such deposits form in 3K mouse brain. We analyze
pathways induced by GBA overexpression implicated in α-synuclein tetramerization and clearance.

Contact Information

Ann Romney Center for Neurologic Diseases
Brigham and Womens Hospital, Harvard Medical School
BTM 10006.10; Room 10006.N
60 Fenwood Road
Boston, MA 02115-6128
p: 617 525 5513