Prof. Dan Frenkel

Research area: Neuroimmunology, Neurodegeneration, Brain metabolism, Aging.
 

Current Research Topics:  The research is focus on glia cells activity to support brain activity in normal condition and in the process of aging.  Special focus is given to the role of glia in supporting essential brain metabolism using different mouse models such of stroke, Alzheimer's disease, Parkinson’s disease Huntington’s disease and multiple sclerosis.

Methods & Techniques: Neurobiology, Immunology, Metabolism, Cell biology, Molecular biology, Histology.

The  research in the laboratory focus  on glial-neuronal cell interactions to clarify their role in neurological diseases, both in culture and in animal models of different neurological diseases. The research is focus on the link between diabetes to neurological diseases. The laboratory combines approaches such as molecular biology, immunological approaches, histological approach, and behavioral approach to shed light on the genes and proteins involved in glial cell function, in particular microglia and astrocyte, in neurodegenerative diseases. The laboratory developed novel approaches to isolate adult glia from mice and to investigate their genetic and proteins profile that relate to pathological condition. Research focus on the link of glia failure to support brain metabolism in aging to the development neurodegenerative diseases. The laboratory develop and investigate new therapeutic approaches to treat neurological diseases such as Alzheimer’s disease and Parkinson’s diseases and has several approved patents.

Levy H, Assaf Y, Frenkel D. Characterization of brain lesions in a mouse model of progressive multiple sclerosis. Exp Neurol. 2010 226(1):148-58.

Farfara D., Trudler D., Amzaleg-Segev  N., Galron R., Stein R., Frenkel D. Gamma-secretase component presenilin mediates microglia beta amyloid clearance. Ann Neurology, 2011, 69(1):170-80. doi: 10.1002/ana.22191.

Weiss  R. Lifshitz  V, Frenkel  D. TGF-β1 affects endothelial cell interaction with macrophage and Th1 T-cells leading to the development of cerebrovascular amyloidosis”Brain Behav Immun.2011 Jul;25(5):1017-24

Lifshitz V., Benromano T., Kfir E.,  Blumenfeld-Katzir T. , Tempel-Brami  C. Assaf   Y., Xia  W., Wyss-Coray  T., Weiner  HL, and Frenkel  D.. “Immunotherapy of cereberovascular amloidosis in a transgenic mouse model” , Neurobiology of aging, 2012  33(2):432.e1-432.e13

Levy-Barazany H. , Frenkel D. “Expression of Scavenger receptor A on antigen presenting cells is important for CD4+T-cells proliferation in EAE mouse model.” Journal of Neuroinflammation 2012, 9:120doi: 10.1186/1742-2094-9-120.

Segev-Amzaleg N, Trudler D, Frenkel D.Preconditioning to mild oxidative stress mediates astroglialneuroprotection in an IL-10-dependent manner. Brain Behav Immun. 2013 30: 176-185

Trudler D, Weinreb O, Mandel SA, Youdim MB, Frenkel D. DJ-1 deficiency triggers microglia sensitivity to dopamine toward a pro-inflammatory phenotype that is attenuated by rasagiline. J Neurochem. 2014;129(3):434-47.

Iram T., Byrne MH, Coleman UA, Kingery ND, Ramirez-Ortiz Z, Means TK, Frenkel D, El Khoury J.MEGF10 IS A RECEPTOR FOR C1Q AND MEDIATES CLEARANCE OF APOPTOTIC CELLS BY ASTROCYTES. Journal of Neuroscience (2016) 11;36(19):5185-92.

Iram T, Trudler D, Kain D, Kanner S, Galron R, Vassar R, Barzilai A, Blinder P, Fishelson Z, Frenkel D. Astrocytes from old Alzheimer's disease mice are impaired in Aβ uptake and in neuroprotection. Neurobiol Dis. 2016;96:84-94.

Nash Y, Schmukler E, Trudler D, Pinkas-Kramarski R, Frenkel D. DJ-1 deficiency impairs autophagy and reduces alpha-synuclein phagocytosis by microglia. J Neurochem. 2017 :143(5):584-594.

Trudler D, Levy-Barazany H, Nash Y, Samuel L, Sharon R, Frenkel D. Alpha synuclein deficiency increases CD4+ T-cells pro-inflammatory profile in a Nurr1-dependent manner. J Neurochem. 2020;152(1):61–71. doi:10.1111/jnc.14871.
 

Frenkel D.  Alzheimer's disease: A need for personalized therapeutic approaches. Drug Dev Res. 2020 Apr;81(2):141-143. doi: 10.1002/ddr.21652.

 
Lazdon E, Stolero N, Frenkel D. Microglia and Parkinson's disease: footprints to pathology. J Neural Transm (Vienna). 2020 Feb;127(2):149-158. 
 

Stolero N, Frenkel D. The dialog between neurons and microglia in Alzheimer's disease: The neurotransmitters view. J Neurochem. 2020 Dec 12. doi: 10.1111/jnc.15262. 
 

Sofer Y, Nash Y, Osher E, Fursht O, Goldsmith G, Nahary L, Shaklai S, Tordjman KM, Serebro M, Touati EB, Yacobi Bach M, Marcus Y, Tal B, Sack J, Shefer G, Margaliot M, Landis N, Goldiner I, Abu Ahmad W, Stern N, Benhar I, Frenkel D. Insulin-degrading enzyme higher in subjects with metabolic syndrome. Endocrine. 2021 Feb;71(2):357-364. doi: 10.1007/s12020-020-02548-2. 
 

Nash Y, Ganoth A, Borenstein-Auerbach N, Levy-Barazany H, Goldsmith G, Kopelevich A, Pozyuchenko K, Sakhneny L, Lazdon E, Blanga-Kanfi S, Alhadeff R, Benromano T, Landsman L, Tsfadia Y, Frenkel D. From virus to diabetes therapy: Characterization of a specific insulin-degrading enzyme inhibitor for diabetes treatment. FASEB J. 2021 May;35(5):e21374. doi: 10.1096/fj.201901945R.