This 850.000 euro grant will allow him to expand his research team and gain fundamental new insights into the mechanisms and role of mRNA localization and local protein during the formation of synapses.
Each neuron in our brain forms thousands of synapses with other neurons that allows neuron communication. Each of these synapses requires hundreds of proteins that allow neurons to communicate with each other. While we now know which proteins are present in these synapses, it remains a great mystery how each neuron manages to bring these hundreds of proteins together in the right place and at the right time to form all these synapses. It is essential that we understand this because we know it goes wrong in neurological diseases.
In this project, his group will use innovative molecular techniques and live-cell and super-resolution imaging to study the role and mechanisms of mRNA localization and protein production in building new synapses at the right time and place. In addition, they will develop a new method to control these processes in neurons which would allow them to guide synapse formation.
New positions for a PhD student and postdoc will become available next year. For this, keep an eye on the team’s website: https://cncr.nl/research-team/neuronal_mrna_trafficking_and_local_translation/
More information on this VIDI project can be found at: https://vu.nl/en/news/2025/vidi-for-max-koppers-the-role-of-local-protein-production-in-synapse-formation
This community-driven data commons – built in collaboration with a broad network of (international) collaborators – integrates lipidomics from human and mouse brain tissue as well as induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, and microglia.
Using this resource, the authors show that iPSC-derived brain cell types display distinct lipid “fingerprints” that closely mirror those found in living tissue. One striking discovery is that the Alzheimer’s disease (AD) risk gene ApoE4 promotes cholesterol ester buildup specifically in astrocytes, a finding that aligns with lipid changes seen in human Alzheimer’s brain samples. Further analysis revealed that altered cholesterol metabolism in astrocytes directly affects immune-related pathways, including the immunoproteasome and antigen presentation systems. Strikingly these immune pathways were downregulated in the cholesterol ester accumulating ApoE4 astrocytes, challenging the view that the AD risk mutation ApoE4 increases glial reactivity and suggesting that immune responses may help protect against AD development.
By making these data openly accessible, the Neurolipid Atlas offers researchers an unprecedented platform to explore lipid dysregulation in brain disorders and accelerate discoveries into the molecular underpinnings of neurodegeneration.
The study is now published in Nature Metabolism and can be found here: https://www.nature.com/articles/s42255-025-01365-z
The mechanisms driving neurodegeneration in Parkinson’s remain incompletely understood, and disease-modifying therapies are still lacking. Although genetic forms of Parkinson’s are rare, they have provided crucial insights into disease mechanisms.
This project will be led by Dr. Ana Carreras Mascaro, who will investigate how specific genetic variants in Parkinson’s disease contribute to neurodegeneration in a physiologically relevant context. Building on Neurospector’s optimized human dopaminergic neuron cultures, she will develop new cell models to study early-onset, genetically driven Parkinson’s.
This research aims to uncover novel pathways involved in neurodegeneration and ultimately support the development of future therapeutic strategies.
Dr. Sanne Beerens (Memory Circuits team) will investigate how different intensities of aversive experiences alter synaptic properties of engram neurons in the prefrontal cortex. This could explain why traumatic memories in PTSD are so persistent while other fear memories fade.
Dr. Janina Kupke (Memory Circuits & Molecular Engram teams) will study whether DNA methylation, a lasting chemical mark on DNA, helps engram neurons maintain stable synaptic connections over time. Using advanced genetic tools and synapse-specific proteomics, she will map the protein landscape of engram synapses to reveal the molecular signatures that keep memories alive.
By revealing how engram neurons store and adapt memories, these projects aim to uncover new targets that may be new entry points for treatment of memory loss in Alzheimer’s disease, age-related cognitive decline, and the persistence of traumatic memories in PTSD.
Stressful experiences are generally remembered well, but such memories are often less precise, which results in memory generalization (recall of the stressful event when this is not relevant). This effect is mediated by stress-hormones. We will investigate how stress-hormones enhance memory generalization by studying the properties of the specific cells in the brain that store a memory, so-called engram cells. For this, we examine their specific cellular properties, their connections, and how we can reverse the effects of stress hormones to prevent memory generalization.
Neurons secrete chemical signal by two main principles: neurotransmitter release from synaptic vesicles (SVs) and neuropeptides from dense-core vesicles (DCVs). The presynaptic proteins RIM and MUNC13 play key roles in both pathways. However, it was still unclear how DCVs are targeted to release sites and whether RIM and MUNC13 are involved in this process. In the current study, Fiona Murphy and team show that three membrane-binding domains in RIM and MUNC13 regulate neuropeptide secretion and do so in a manner that is different from the way these same protein regulate neurotransmitter release.
Using neuropeptide secretion assays with single-vesicle resolution and peptidomics analysis of endogenous neuropeptide release in MUNC13/RIM null mutant neurons, the authors demonstrate that MUNC13 is essential for neuropeptide secretion. The N-terminus of RIM prevents MUNC13 degradation via the proteasome, and inhibiting proteasomal degradation partially restored neuropeptide secretion in RIM’s absence. RIM and MUNC13 both contain a C2 domain, a protein domain known to bind/recruit specific positively charged phospholipids in the plasma membrane (PIP2) that are known to be important for the membrane fusion reaction. The RIM C2 domain and the MUNC13 C1-C2B polybasic face are both essential for neurotransmitter release. However, the authors show that the two domains are redundant for neuropeptide secretion. In contrast, the lipid-binding MUNC13 C2C domain is essential.
This study shows that RIM and MUNC13 synergistically regulate neuropeptide secretion through membrane interactions and reveal new mechanistic differences between SV and DCV secretion principles.
The study was published in The Journal of Cell Biology and be found here:
This prestigious award is bestowed upon individuals whose groundbreaking scientific contributions have significantly advanced our understanding of STXBP1-related disorders. Prof. Verhage’s long-standing dedication to translational research has been instrumental in uncovering critical disease mechanisms in SNAREopathies, particularly STXBP1. His tireless efforts have not only expanded our scientific knowledge but also paved the way for potential new therapies, offering hope to countless families affected by these conditions.
We are incredibly proud to have Prof. Verhage’s expertise and leadership within the STXBP1 community. His work continues to inspire progress and innovation in the field of rare disease research.
While Prof. Verhage was unable to attend this year’s STXBP1 Summit + Family Meeting in Colorado organized by the STBPX1 Foundation, they celebrated his achievements with a special award ceremony. A short acceptance video from Prof. Verhage was shared during the event, which allowed the attendees to honor his remarkable accomplishments and contributions to the field.
Please join us in congratulating Prof. Verhage on this well-deserved recognition. His passion and dedication to advancing the understanding of STXBP1-related disorders have made a profound impact on both the scientific community and families worldwide.
Acceptance video of Innovative Research Award by Verhage lab.
The Locus Coeruleus (LC) is the brain’s main source of noradrenaline (NA) and a key “first responder” to stressful events. In challenging situations (e.g., fearful or anxiogenic environments), the LC-NA system drives critical functions such as arousal, attention, and decision-making, triggering rapid “fight-or-flight” responses. When this system becomes overactive, it can lead to heightened stress reactivity and contribute to conditions like anxiety disorders.
The researchers (Neuromodulation of Cognition) hypothesized that peptidergic neuromodulation might act as a natural brake on LC activity, thereby keeping our stress response in check. To investigate this, they used a combination of advanced techniques – genetic labelling, viral tracing, electrophysiology, imaging of peptide release dynamics, and in vivo chemogenetic and pharmacological interventions. They discovered a previously unknown group of Neuropeptide Y (NPY)-expressing neurons that surround the LC. These peri-LC NPY cells form inhibitory connections with LC neurons, dampening their activity. When the team activated or silenced these cells, they saw corresponding changes in anxiety-like behaviours, showing that this local NPY system plays a direct role in modulating the stress response.
Collectively, this work reveals a new circuit-level mechanism for how the brain responds to adversity, highlighting the importance of endogenous peptidergic signalling in maintaining adaptive responses to stress.
The ADORE Centre (Amsterdam Oncology and Neuroscience Research) is a pioneering facility, the first of its kind to establish a structural collaboration between cancer and neuroscience experts. By integrating the fields of neurology and oncology, ADORE fosters interdisciplinary partnerships and promotes the exchange of knowledge, accelerating the development of innovative healthcare solutions for a broad range of patients.
At the heart of ADORE’s research is the TRANSVISION project, which employs ultra-sensitive technologies to study cell-to-cell communication at the level of individual cells. Researchers are particularly focused on how tumor cells and brain cells interact, aiming to pinpoint the proteins involved in these exchanges. This deeper understanding could unlock new, precisely targeted treatment strategies.
“The better we understand how cells ‘talk’ to each other, the more precisely we can intervene and develop new medications,” said Guus Smit, Director of Neuroscience Research at ADORE.
During the opening ceremony, several researchers from the CNCR had the opportunity to engage with Queen Máxima. Among them was postdoctoral researcher Ana Carreras Mascaro from the Neurospector team, who gave the Queen a glimpse of our cultured human neurons through a microscope. Senior researchers Femke Feringa and Rik van der Kant also spoke with Her Majesty, sharing insights from their groundbreaking work on Alzheimer’s disease.
Photography by Mark van den Brink, Amsterdam UMC
Promising step
Rik van der Kant discovered that cholesterol buildup in brain cells of Alzheimer’s patients directly leads to an accumulation of the toxic proteins Tau and Amyloid. He also found that Efavirenz might be suitable for reversing this buildup. Dr. Jort Vijverberg, Neurologist at the Alzheimer Center is also hopeful about the trial “We are very curious to see how this medication will work in Alzheimer’s patients, I consider it a promising step in the right direction.”
Participants needed
The trial is still looking for participants. In total, forty patients are needed to take part in the three-month clinical trial in Amsterdam. Participants can take part if they have been diagnosed with early-stage Alzheimer’s disease, are between 50 and 75 years old, and have a family member or caregiver who can accompany them to the research center visits and answer questions about their health and daily functioning. If participants are unsure whether they want to or are able to take part, they can always register without obligation. Their eligibility to participate will be assessed at a later stage.”
For more information, visit Efavirenz – Brain Research Center