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Updated: May 11, 2026
Human Neural Organoids for Studying Brain Cancer and Neurodegenerative Diseases
Published on: June 28, 2019
ATM-deficient human neural stem cells as an in vitro model system to study neurodegeneration
Luigi Carlessi1, Elena Fusar Poli, Lidia De Filippis
1Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133, Milan, Italy.
Abstract:
Loss of ATM kinase, a transducer of the DNA damage response and redox sensor, causes the neurodegenerative disorder ataxia-telangiectasia (A-T). While a great deal of progress has been made in elucidating the ATM-dependent DNA damage response (DDR) network, a key challenge remains in understanding the selective susceptibility of the nervous system to faulty DDR. Several factors appear implicated in the neurodegenerative phenotype in A-T, but which of them plays a crucial role remains unclear, especially since mouse models of A-T do not fully mirror the respective human syndrome. Therefore, a number of human neural stem cell (hNSC) systems have been developed to get an insight into the molecular mechanisms of neurodegeneration as consequence of ATM inactivation. Here we review the hNSC systems developed by us an others to model A-T.
Insights
Ataxia-telangiectasia (A-T) is a neurodegenerative disorder caused by ATM kinase loss. This review discusses human neural stem cell (hNSC) models used to understand A-T
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Ataxia-telangiectasia (A-T) is a neurodegenerative disorder linked to ATM kinase dysfunction.
- ATM kinase is crucial for DNA damage response and redox sensing.
- The nervous system's specific vulnerability to DNA damage response defects is not fully understood.
Purpose of the Study:
- To review human neural stem cell (hNSC) systems developed for modeling A-T.
- To gain insight into the molecular mechanisms of neurodegeneration resulting from ATM inactivation.
Main Methods:
- Review of existing literature on hNSC models for A-T.
- Analysis of studies utilizing hNSC systems to investigate ATM deficiency.
Main Results:
- hNSC systems offer a valuable platform for studying A-T pathogenesis.
- These models help elucidate the role of ATM in neuronal development and maintenance.
- Mouse models do not fully recapitulate the human A-T syndrome, highlighting the need for hNSC systems.
Conclusions:
- Human neural stem cell models are essential for understanding ATM deficiency in neurodegeneration.
- Further research using hNSC systems will clarify the molecular underpinnings of A-T.
- These models facilitate the development of targeted therapeutic strategies for A-T.
