Neurodegeneration

• Alzheimer's disease (AD) is the most common neurodegenerative disorder. We have used Drosophila melanogaster  to study the link between AD risk genes and the tau protein. We also discovered a role for tau in chromosomal instability.

•  Amytrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) belong to a spectrum of severe neurodegenerative disorders in which the TDP-43 protein plays a central role. We study TDP-43 in Drosophila melanogaster and human cells and have discovered a novel role for TDP-43 in muscle degeneration. 

• Mutations in RNF216 cause a form of ataxia, dementia and hypogonadism called Gordon Holmes syndrome, characterized by ubiquitin-positive neuronal inclusions. We discovered that this disorder can also present as a Huntington-like disorder and are studying the function of RNF216 and its role in inclusion formation.

Selected publications

C-terminal frameshift variant of TDP-43 with pronounced aggregation-propensity causes rimmed vacuole myopathy but not ALS/FTD. 

Ervilha Pereira P*, Schuermans N*, Meylemans A, LeBlanc P, Versluys L, Copley KE, Rubien JD, Altheimer C, Peetermans M, Debackere E, Vanakker O, Janssens S, Baets J, Verhoeven K, Lammens M, Symoens S, De Paepe B, Barmada SJ, Shorter J, De Bleecker JL, Bogaert E, Dermaut B.
Acta Neuropathol. 2023 Mar 31. doi: 10.1007/s00401-023-02565-1. PMID: 37000196.

Expanding the TDP-43 Proteinopathy Pathway From Neurons to Muscle: Physiological and Pathophysiological Functions.

Versluys L, Ervilha Pereira P, Schuermans N, De Paepe B, De Bleecker JL, Bogaert E, Dermaut B.

Front Neurosci. 2022 Feb 3;16:815765. doi: 10.3389/fnins.2022.815765. eCollection 2022. 

PMID: 35185458

Developmental Expression of 4-Repeat-Tau Induces Neuronal Aneuploidy in Drosophila Tauopathy Models.

Malmanche N, Dourlen P, Gistelinck M, Demiautte F, Link N, Dupont C, Vanden Broeck L, Werkmeister E, Amouyel P, Bongiovanni A, Bauderlique H, Moechars D, Royou A, Bellen HJ, Lafont F, Callaerts P, Lambert JC, Dermaut B.

Sci Rep. 2017 Jan 23;7:40764. doi: 10.1038/srep40764.

PMID: 28112163

RNF216 mutations as a novel cause of autosomal recessive Huntington-like disorder.

Santens P, Van Damme T, Steyaert W, Willaert A, Sablonnière B, De Paepe A, Coucke PJ, Dermaut B.

Neurology. 2015 Apr 28;84(17):1760-6. doi: 10.1212/WNL.0000000000001521. Epub 2015 Apr 3.

PMID: 25841028

TDP-43-mediated neurodegeneration: towards a loss-of-function hypothesis? 

Vanden Broeck L, Callaerts P, Dermaut B.

Trends Mol Med. 2014 Feb;20(2):66-71. doi: 10.1016/j.molmed.2013.11.003. Epub 2013 Dec 16.

PMID: 24355761

TDP-43 loss-of-function causes neuronal loss due to defective steroid receptor-mediated gene program switching in Drosophila.

Vanden Broeck L, Naval-Sánchez M, Adachi Y, Diaper D, Dourlen P, Chapuis J, Kleinberger G, Gistelinck M, Van Broeckhoven C, Lambert JC, Hirth F, Aerts S, Callaerts P, Dermaut B.

Cell Rep. 2013 Jan 31;3(1):160-72. doi: 10.1016/j.celrep.2012.12.014. Epub 2013 Jan 17.

PMID: 23333275

Rare neurological diseases

• Due to their extensive clinical and molecular heterogeneity, rare neurological disorders (RND) in adults are difficult to diagnose. Our lab is strongly involved in the discovery of genetic causes in challenging undiagnosed cases and participates in local (UD-PrOZA) and international rare disease initiatives (ERN-RND, Solve-RD). 

• We have contributed to the discovery of several novel disease genes and created Drosophila models of novel neurological disease genes in collaboration with Solve-RD.

• RNF213 is a susceptibilty gene for Moyamoya disease (MMD), a rare cerebrovascular disorder with unknown etiology. In collaboration with Prof. dr. Francis Impens we are studying the role of immune-related responses such as infections to trigger MMD onset.

Selected publications

Loss of phospholipase PLAAT3 causes mixed lipodystrophic and neurological syndrome due to impaired PPARγ signaling

Schuermans N, El Chehadeh S, Hemelsoet D, Gautheron J, Vantyghem MC, Nouioua S, Tazir M, Vigouroux C, Auclair M, Bogaert E, Dufour S, Okawa F, Hilbert P, Van Doninck N, Taquet MC, Rosseel T, De Clercq G, Debackere E, Van Haverbeke C, Cherif FR, Urtizberea JA, Chanson JB, Funalot B, Authier FJ, Kaya S, Terryn W, Callens S, Depypere B, Van Dorpe J, Program for Undiagnosed Diseases (UD-PrOZA), Poppe B, Impens F, Mizushima N, Depienne C, Jéru I, Dermaut B

Nat Genet. 2023 Nov 02 55(11):1929-1940. doi: 10.1038/s41588-023-01535-3
PMID: 37919452

Shortcutting the diagnostic odyssey: the multidisciplinary Program for Undiagnosed Rare Diseases in adults (UD-PrOZA).

Schuermans N, Hemelsoet D, Terryn W, Steyaert S, Van Coster R, Coucke PJ, Steyaert W, Callewaert B, Bogaert E, Verloo P, Vanlander AV, Debackere E, Ghijsels J, LeBlanc P, Verdin H, Naesens L, Haerynck F, Callens S, Dermaut B, Poppe B; for UD-PrOZA.

Orphanet J Rare Dis. 2022 May 23;17(1):210. doi: 10.1186/s13023-022-02365-y.

PMID: 35606766

Proteome Profiling of RNF213 Depleted Cells Reveals Nitric Oxide Regulator DDAH1 Antilisterial Activity.

Martina L, Asselman C, Thery F, Boucher K, Delhaye L, Maia TM, Dermaut B, Eyckerman S, Impens F.

Front Cell Infect Microbiol. 2021 Nov 3;11:735416. doi: 10.3389/fcimb.2021.735416. eCollection 2021.

PMID: 34804992

Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity.
Thery F, Martina L, Asselman C, Zhang Y, Vessely M, Repo H, Sedeyn K, Moschonas GD, Bredow C, Teo QW, Zhang J, Leandro K, Eggermont D, De Sutter D, Boucher K, Hochepied T, Festjens N, Callewaert N, Saelens X, Dermaut B, Knobeloch KP, Beling A, Sanyal S, Radoshevich L, Eyckerman S, Impens F.
Nat Commun. 2021 Oct 1;12(1):5772. doi: 10.1038/s41467-021-26061-w.
PMID: 34599178

Moyamoya disease emerging as an immune-related angiopathy.
Asselman C, Hemelsoet D, Eggermon D, Dermaut B*, Impens F*
Trends in Molecular Medicine, September 14, 2022 - online ahead of print doi:https://doi.org/10.1016/j.molmed.2022.08.009  *shared last authorship