Date and Venue
Friday 09/05/2025 · 09:00h – 16:00 h
Sala Baobab, Tower I, Floor 11 (PCB)
The first workshop on May 9th will focus on will focus on exploring the molecular and cellular mechanisms of neurodegeneration and CNS pathology, as well as emerging therapies and prevention strategies. The event will feature two plenary lectures by leading external experts, along with a series of presentations by IBEC researchers.
Amaia Arranz (Achucarro Basque Center for Neuroscience) – Investigating how APOE variants influence astrocyte function in Alzheimer’s disease using humanized in vitro models and chimeric mice.
Salvador Ventura (Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona) – Exploring protein folding, misfolding, and aggregation in Parkinson’s and other neurodegenerative diseases.
We will also have three presentations from IBEC researchers working in the field and a final roundtable discussion on how these novel concepts and approaches can drive new therapeutic strategies and prevention for CNS disorders.
Schedule programme:
9:00 – Registration
9:20 – Welcome from Network Coordinator
9:30 – Mariano Martín, IBEC, “Amyloids ‘at the border’: deep mutagenesis and random sequence extension reveal an incomplete amyloid-forming motif in Bri2 that turns amyloidogenic upon C-terminal extension”
10:00 – Invited speaker: Salvador Ventura, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, “A structure-based approach to tackle protein aggregation in Parkinson’s disease”
11:00 – Coffee Break and Networking
11:30 – Invited speaker: Amaia Arranz, Achucarro Basque Center for Neuroscience, “Divergent Effects of APOE3 and APOE4 Human Astrocytes on Key Alzheimer’s Disease Hallmarks in Chimeric Mice”
12:30 – Roundtable moderated by network chairs to debate the issues discussed
13:30 – Lunch break
14:30 – Amayra Hernández, IBEC, “Dynamics of Axonal Degeneration in Alzheimer’s Disease Induced by Tau or Amyloid Beta Aggregation”
15:00 – Karolina Zimkowska, IBEC, “Neuronal Activity and p-Tau: Lessons from Primary Cultures to Cortical Organoids Modeling FTLD-17”
15:30 – Closing remarks and end of the workshop
Plenary talks details:
Amaia Arranz (Achucarro Basque Center for Neuroscience)
Divergent Effects of APOE3 and APOE4 Human Astrocytes on Key Alzheimer’s Disease Hallmarks in Chimeric Mice
Despite strong evidence supporting that both astrocytes and apolipoprotein E (APOE) play crucial roles in the pathogenesis and progression of Alzheimer’s disease (AD), the impact of astrocytes carrying different APOE variants on key AD pathological hallmarks remains largely unknown. To explore such effects in a human relevant context, we generated a chimeric model of AD. We transplanted isogenic APOE3 or APOE4 human induced pluripotent stem cell (hiPSC)-derived astrocyte progenitors into neonatal brains of AD model mice. We show that at five to six months after transplantation, transplanted cells have differentiated into mature astrocytes (h-astrocytes) that often integrate in upper layers of one cortical hemisphere. APOE3 and APOE4 h-astrocytes differentially express and secrete the APOE protein, which binds to Aβ plaques with an isoform-dependent affinity. Remarkably, APOE3 h-astrocytes ameliorate Aβ pathology, Tau pathology and neuritic dystrophy. In contrast, APOE4 h-astrocytes aggravate these AD processes. Moreover, APOE3 and APOE4 h-astrocytes modulate microglia responses to Aβ pathology in opposite ways. APOE4 h-astrocytes enhance microglia clustering around Aβ plaques and exacerbate DAM state whereas APOE3 h-astrocytes reduce microglia clustering and induce a more homeostatic state on plaque-associated microglia. These findings highlight a critical contribution of h-astrocytes not only to Aβ pathology but also to other key AD hallmarks in chimeric mice. In addition, our findings reveal that h-astrocytes with different APOE variants and the different forms of APOE they secrete have a crucial role in AD progression.
Salvador Ventura (Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona)
A Structure-Based Approach to Tackle Protein Aggregation in Parkinson’s Disease
α-Synuclein aggregation drives neurodegeneration in Parkinson’s disease (PD). We identified peptides that selectively bind to toxic α-synuclein oligomers and fibrils with high affinity while sparing the functional monomer. These peptides effectively inhibit aggregation and prevent oligomer-induced cell damage. Human peptide candidates with strong anti-aggregation and detoxifying properties were discovered, and the best in vitro candidate alleviated motor symptoms in a PD animal model. Structural studies mapped their binding region, showing that mutations or deletions in this site eliminate α-synuclein aggregation and toxicity. This insight led to the development of conformation-specific nanobodies and monoclonal antibodies that block amyloid formation, providing a novel therapeutic and diagnostic strategy for PD.
