Team 1

Proteinopathies of the nervous system

Our research axes

Protein misfolding is the cause of a wide range of central and peripheral nervous system diseases. Our team evaluates the impact of misfolded protein deposits on the nervous system and proposes various therapeutic avenues. We focus on aggregated proteins linked to Alzheimer’s disease (Tau and Aβ42), dementia with Lewy bodies (alpha-synuclein), and transtyrethin amyloid neuropathy. We focus on four major research lines

1. The insvestigation of mechanisms of formation and spreading of misfolded proteins: towards therapies for amyloidogenic proteinopathies
2. Mechanisms leading to the toxicity of misfolded proteins with a focus on the cross-talk between misfolded proteins and synapses
3. The interaction between misfolded proteins and neuroinflammation
4. The interaction between neurosteroids and neurodegenerative proteinopathies

Selected publications

• Adams D, Algalarrondo V, Echaniz-Laguna A. Hereditary transthyretin amyloidosis in the era of RNA interference, antisense oligonucleotide, and CRISPR-Cas9 treatments. Blood. 2023 Nov 9;142(19):1600-1612. https://doi.org/10.1182/blood.2023019884
• Akwa Y, Di Malta C, Zallo F, Gondard E, Lunati A, Diaz-de-Grenu LZ, Zampelli A, Boiret A, Santamaria S, Martinez-Preciado M, Cortese K, Kordower JH, Matute C, Lozano AM, Capetillo-Zarate E, Vaccari T, Settembre C, Baulieu EE, Tampellini D. Stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau in cellular and mouse models of tauopathies. Autophagy. 2023 Feb;19(2):660-677. https://doi.org/10.1080/15548627.2022.2095791
• Bousset L, Alik A, Arteni A, Böckmann A, Meier BH, Melki R. α-Synuclein Fibril, Ribbon and Fibril-91 Amyloid Polymorphs Generation for Structural Studies. Methods Mol Biol. 2023;2551:345-355. https://doi.org/10.1007/978-1-0716-2597-2_23
• Boutary S, Khalaf G, Landesman Y, Madani ME, Desmaële D, Piguet F, Alonso R, Banchi EG, Adams D, Massaad C, Massaad-Massade L Therapeutic potential of siRNA PMP22-SQ nanoparticles for Charcot-Marie-Tooth 1A neuropathy in rodents and non-human primates.  Int J Pharm. 2025 Feb 25;671:125234. https://doi.org/10.1016/j.ijpharm.2025.125234
• Célestine M, Jacquier-Sarlin M, Borel E, Petit F, Lante F, Bousset L, Hérard AS, Buisson A, Dhenain M. Transmissible long-term neuroprotective and pro-cognitive effects of 1-42 beta-amyloid with A2T icelandic mutation in an Alzheimer’s disease mouse model. Mol Psychiatry. 2024 Dec;29(12):3707-3721. https://doi.org/10.1038/s41380-024-02611-8
• Kabani M. Extracellular Vesicles-Encapsulated Yeast Prions and What They Can Tell Us about the Physical Nature of Propagons. Int J Mol Sci. 2020 Dec 23;22(1):90. https://doi.org/10.3390/ijms22010090
• Lam S, Petit F, Hérard AS, Boluda S, Eddarkaoui S, Guillermier M; Brain Bank Neuro-C. E. B. Neuropathology Network; Buée L, Duyckaerts C, Haïk S, Picq JL, Dhenain M. Transmission of amyloid-beta and tau pathologies is associated with cognitive impairments in a primate. Acta Neuropathol Commun. 2021 Oct 12;9(1):165. https://doi.org/10.1186/s40478-021-01266-8
• Wiessler AL, Hasenmüller AS, Fuhl I, Mille C, Cortes Campo O, Reinhard N, Schenk J, Heinze KG, Schaefer N, Specht CG, Villmann C. Role of the Glycine Receptor β Subunit in Synaptic Localization and Pathogenicity in Severe Startle Disease. J Neurosci. 2024 Jan 10;44(2):e0837232023. https://doi.org/10.1523/JNEUROSCI.0837-23.2023