Full Grants

• Prof. Moshe Parnas | Sagol School of Neuroscience
   
• Prof. Mia Horowitz  | Emeritus George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology

In the present proposal we will address how the genetic interplay between mGBA1 and mLRRK2 affects PD severity. The specific aims are:

1. Generalize the interaction between mGBA1 and mLRRK. We have shown the interplay between mGBA1 and mLRRK2 using I2020T and G2019S mLRRK2 variants and L444P and N370S mGBA1 variants. We would like to use other mGBA1 variants which are important in the study of PD: E326K and R496H. We also wish to test a mutation in the SMPD1 gene, associated with Neimann-Pick disease, and with PD.
    
2. Study ERAD, UPR and the behavioral consequences of the different mutation combinations. We would like to confirm the amelioration of ERAD and UPR in the double mutant flies due to the protective effect of mLRRK2. We also wish to establish behavioral changes associated with PD, like: loss of smell and loss of cognition.
    
3. Study the molecular mechanisms underlying the interplay between mGBA1 and mLRRK2. We will test which is the mechanism underlying the increased mLRRK2-mediated degradation of mGCase. Whether it is proteasoml- or autophagy-related mechanism. Explore >>

Exploring the Role of Rab12, the Enigmatic Player in Parkinson’s Disease, and its Regulation by the Newly Identified Crosstalk between LRRK2 and Protein Kinase Cb

• Prof. Ronit Sagi-Eisenberg | Dept. Human Cell & Development Biology, Gray Faculty of Medical and Health Sciences, Tel Aviv University

Relying on our results that demonstrate a hitherto unknown crosstalk between LRRK2 and PKCb and distinguish the Rab12 complex with RILP, which comprises the non-phosphorylated form of Rab12, from its other complexes, we plan to focus in the present study on the following specific aims:
Ø Aim 1: Investigate the relationship between LRRK2 and PKCb. We aim to identify the specific PKCb isoform that
acts in concert with LRRK2 and explore the underlying mechanism of their crosstalk.
Ø Aim 2: Identify the neuronal organelle(s), whose transport is controlled by the Rab12-RILP complex. We
hypothesize that the level of phosphorylated Rab12 dictates its distribution between its effectors, thereby influencing the transport of Rab12-regulated organelles.
Explore >>

Unraveling Personalized Profiles of Cognitive-Motor Interactions using Naturalistic, Virtual Reality-Based Behaviors in People with Parkinson's Disease

• Jason Friedman | Department of Physical Therapy, Gray Faculty of Medical and Health Sciences
   
• Prof. Meir Plotnik | Departmant of Physiology, Gray Faculty of Medical and Health Sciences; Center of Advanced Technologies in Rehabilitation, Sheba Medical Center
   
• Dr. Benedetta Heimler | Center of Advanced Technologies in Rehabilitation, Sheba Medical Center
  
  Explore >>

REM Sleep Microstructure as a Window for Understanding the Neurobiology of Depression in Parkinson's Disease

• Noham Wolpe | Gray Faculty of Medical and Health Sciences
   
• Rivi Tauman |  Gray Faculty of Medicine, Department of Pediatrics

Our proposal. As REM dysregulation is a key feature of depression, and depression could be an early manifestation of the neurodegenerative process in PD, testing early PD patients with depression provides an opportunity to address key, yet unresolved questions about the mechanisms linking depression and PD. Here, we propose to test this unique patient population in a study that combine the expertise of PI Tauman in sleep microstructure and PI Wolpe in mental health and neurodegenerative conditions. This new collaboration will allow us to combine cognitive neuroscience methods from PI’s Wolpe’s lab to examine reward sensitivity as a key marker in the pathogenesis of depression, while accounting for other neuropsychiatric symptoms common in PD. These methods will be combined with PI Tauman’s expertise in REM sleep microstructure. Our study will be the first, to our knowledge, to examine the relationship between REM sleep measures, depression, and PD. Findings from our study will have broad implications, with REM sleep dysregulation as a potential marker for the neurodegenerative process that contributes to both PD and depression in PD. REM sleep dysregulation could thereby become a candidate target for early interventions aiming to modify the progression of PD. Explore >>