University of Groningen
Cell-autonomous and non-cell autonomous protection of DNAJB6 in Huntington’s disease
Bason, Matteo
DOI:
10.33612/diss.101925993
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Publication date: 2019
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Bason, M. (2019). Cell-autonomous and non-cell autonomous protection of DNAJB6 in Huntington’s disease. University of Groningen. https://doi.org/10.33612/diss.101925993
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STELLINGEN
Cell-autonomous and non-cell autonomous protection of DNAJB6 in Huntington’s disease
By
Matteo Bason
1. Huntington’s is not a purely neuronal disease. Astrocytes are crucial players and can be both friends and foes for neurons in different stages of the disease. A possible therapy might arise from better understanding how to keep astrocytes in a “friendly mood” (this thesis).
2. Protein aggregates in neurodegenerative diseases are toxic through multiple cellular targets: focusing on rescuing only one of these will not save cells from degeneration. To find a cure, we must act on the “roots” and not on the “branches” of the disease (this thesis).
3. Astrocytes can play the role of “reservoir” of prionoids protecting neurons from these toxic species (this
thesis). Intriguingly, this does not apply only to Huntington’s because prion-like spreading of aggregates
is a common aspect in the progression of different brain diseases including Alzheimer’s and Parkinson’s. 4. “Glia expressing mutant huntingtin impart a disease phenotype to normal mice, whereas normal glia
ameliorate the Huntington’s phenotype” (modified after Benraiss et al., Nature Communication, (2016),
7:11758). The transplantation of astrocytes, instead of neurons, could be a less challenging and still efficient approach to slow down the disease progression.
5. Similarly to psychiatry in which “it is easier to build strong children than to repair broken men” (modified after “My Bondage and My Freedom” by Frederick Douglass; Arango et al., Lancet Psychiatry, (2018), 5:591-604), preventive approaches aimed to build a more resilient and resistant brain should be applied to fight neurodegenerative diseases.
6. “It is for your sake, […] Castle Keep […] that I have come back, counting my own life as nothing in the
balance, […]. What do I care for danger now that I am with you? You belong to me, I to you, we are united, what can harm us?”(Franz Kafka, ‘The Burrow’). Patients with mental disorders – so well
represented by the being in the Burrow – often do not receive adequate treatments. To help people to
“escape from the
Castle Keep”, mental problems must not become a social stigma or be underestimated.7. “Progress depends on our brain. The most important part of our brain, that which is neocortical, must be
used to help others and not just to make discoveries” – Rita Levi Montalcini, (‘Le tue antenate. Donne
pioniere nella società e nella scienza dall'antichità ai giorni nostri’, Ed. Gallucci, 2008.)
8. Research and innovation should not be only evaluated in numeric terms (publications, grants, patents and firms). These are indeed important indicators, but we must not forget that science is made by the people behind those numbers. A research for the people and not only for the numbers will lead us towards new discoveries and help to fight scientific misconceptions and mistrusts.
9. To fight unemployment in Italy, the traditional way of teaching in many Italian universities should fundamentally change: less focus on mere memorization to pass “the next exam”, more emphasis on understanding and independent reasoning, to be prepared for what is after graduation.
10. “We are five brothers. We live in different cities, some of us live abroad […]. When we meet, we can be
uninterested or distracted each other, but one word between us is enough […] to find again our old relationships, our childhood and youth, inextricably linked to those sentences […]. Those words are the foundation of our family unity, which will exist as long as we are in the world, recreating and resurrecting in the most diverse parts of the earth” – Natalia Ginzburg (translated from ‘Lessico famigliare’, Torino,
