Neurodegenerative diseases

…discovery approach across multiple diseases, AI-based disease modeling, an

A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord. A major function of TDP-43 is as a repressor of cryptic exon inclusion during RNA splicing. By re-analyzing RNA-sequencing datasets from human FTD/ALS brains, we discovered dozens of novel cryptic splicing events in important neuronal genes. Single nucleotide polymorphisms in UNC13A are among the strongest hits associated with FTD and ALS in human genome-wi

…and epigenetic underpinnings of human diseases such as Parkinson’s, Alzheimer’s, autism, and cancer. Mechanisms of somatic cell reprogramming to an embryonic pluripotent state are explored, utilizing patient-specific pluripotent cells to model and analyze neurodegenerative diseases.

For more than 20 years, a growing body of evidence indicates that the brain functions near a critical point, where neural activity is balanced between damping and amplification. One of the appealing benefits of criticality is its optimal information processing [1, 2]. In addition, deviations from criticality are associated with age and disease [3] but also physiological state [4]. Yet the neural mechanisms involved in maintaining and/or altering this criticality remain unclear. To investigate how cellular mechanisms can influence criticality, we analyze a model of neuronal network [5] and quan

…strategy for a wide range of neurodegenerative diseases. Adeno-associated viruses (AAVs) have demonstrated significant potential as safe and effective vectors for the delivery of therapeutic genes to the CNS. Despite the tremendous promises of AAV-based gene therapies, the pathway to develop these therapies from bench to clinic remains complex and arduous. In response to these challenges, we introduce the BrainVector project, a comprehensive cross-disciplinary platform that streamlines the pre-clinical development of AAV-bas

…of IR inhibition in the treatment of neurodegenerative diseases such as epilepsy underscores the importance of further elucidating its biophysical mechanism. In this study, the effects of IR neuromodulation on cortical neurons in vivo were investigated using high-density laminar recordings. The neocortex of anesthetized rats was exposed

…age-related memory impairment, and neurodegenerative diseases of vertebrates including humans. Using young (3-4

…application against AD and similar neurodegenerative diseases. Exosomes are small particles that can cross biological membranes like the blood-brain barrier. They are being used as drug carrier systems and have attracted attention recently. In AD and similar diseases, exposure to oxidant molecules increases in

Studying the dynamic role of microglia in brain development and neurodegenerative diseases requires models that closely resemble the human brain environment. While murine models provide valuable insights, they often have important transcriptional and cellular differences from humans. Addressing this, we developed a chimeric in vitro model to study microglial behavior within a human-like neuronal setting.We co-cultured human iPSC-derived human organoids (hORG) with mouse brain slice cultures (mBSC). In this chimeric setup we found multiple interactions between mouse and human tissue, markedly a

Aging and neurodegenerative diseases, such as Alzheimer's (AD) or Amyotrophic Lateral Sclerosis (ALS), led to widespread degeneration of long-range connections in cortical structural connectivity (SC). These damages manifest as losses in connections or demyelination of axons. When the SC of the brain is damaged, the functional connectivity (FC, i.e. the dynamic interactions and information exchange between distinct brain regions) is locally and globally perturbed. Despite the close correlation between SC and FC, they are not identical; FC exhibits greater flexibility and can reorganize in resp

…to the brain for the treatment of neurodegenerative diseases is a great challenge because of the blood-brain barrier selectivity. However, nanoliposomal systems can provide an alternative to this drawback. This study aimed to design and develop nanoliposomes based on soy lecithin loaded with galantamine (acetylcholinesterase inhibitor) or DNA aptamers designed to hinder the aggregation of proteins like Aβ, TDP-43 and α-synuclein. For this, a complete physicochemical characterization of soy lecithin and other raw materials was carried

…development and progression of many neurodegenerative diseases, such as Alzheimer’s Disease (AD). However, most in vitro BBB models are static, complicating the understanding of disease pathophysiology. With that, our study aims to develop a microfluidic device to better study the relationship between neurodegenerative diseases and the BBB in vitro. The device, printed using polydimethylsiloxane, includes a compartment for a hydrogel containing neurons and astrocytes to mimic cerebral parenchyma and a m

…abilities are a major risk factor for neurodegenerative diseases. Dietary restriction (DR) can slow or postpone these changes, improving memory, learning, and cognitive abilities, but may not always yield positive results. In this study, we examined the impact of 30% DR (70% of ad libitum daily intake) during adolescence on the short-term (STM) and long-term (LTM) memory performance in 6- and 18-month-old female Wistar rats. The effects of DR were examined in three onsets and durations: DR1 (28th to 35th day of life), DR2 (35th to 42nd day

…is a risk factor in the development of neurodegenerative diseases, neuropsychiatric disorders and is associated with cognitive decline. DREAM/kchip3/calsenilin (DREAM) is a multifunctional protein that belongs to the neuronal Ca2+ sensor family. Previous studies have demonstrated the relevance of DREAM in nociception and in learning and memor

Clinical data strongly support olfactory impairment as an early indicator of neurodegenerative diseases (ND), including Alzheimer’s disease. In AD patients, neurofibrillary tangles (NFTs) have been identified in the entorhinal cortex and olfactory bulbs, both crucial in olfactory information processing. We therefore investigated the hypothesis that typical ND lesions could appear early in olfactory system regions.We used a tauopathy mouse model (PS19 mice) expressing the human tau protein (1N4R) carrying the P301S mutation. PS19 mice develop NFTs-like inclusions at six months, leading to progr

…in humans have been linked to several neurodegenerative diseases, including spinal muscular atrophy associated with microcephaly and impaired cognitive and motor function. Thus, it has been identified as potentially involved in the maintenance and development of the nervous system. However, precise pathophysiological mechanisms and VRK1 involvement in cognitive and motor dysfunction progression have yet to

…commonly occur in normal aging and neurodegenerative diseases, highlighting the importance of understanding the underlying mechanisms to inform potential interventions. Brain regions active during PM tasks include the left dorsolateral prefrontal cortex (DLPFC) and inferior parietal cortex. PM tasks engage attentional networks, and changes in alpha frequency oscillations were observed during PM processing. We hypothesized that these

Progressive myoclonus epilepsies (PMEs) represent a group of epilepsy disorders that begin in adolescence and are inherited in an autosomal recessive manner. PME patients exhibit a range of symptoms, including seizures, ataxia, muscle atrophy, dementia, psychosis, and hallucinations. The majority of these subsequent symptoms are likewise observed in older individuals, indicating the potential involvement of the PME genes in the process of aging. A recent study conducted by our group has shown that the expression of PME genes shows an inverse association with age in the normal brain. Since the

Recently found association linking viral infections to neurodegenerative diseases has raised concerns about unknown mechanisms in the communication between the respiratory and central nervous systems . We hypothesized that extracellular vesicles (EVs) can transfer viral signals to microglia, triggering the upregulation of pro-inflammatory cytokines by activating inflammasome-related pathways. In this study, we investigate the role of EVs released from virus mimetic poly I:C-infected human airway epithelial cells in modulating microglial immune responses. EVs were isolated from poly I:C-primed

…activity for neuroinflammatory and neurodegenerative diseases, such as multiple sclerosis (MS) and Alzheimer´s disease (AD). The CSF is the compartment in closest proximity to the central nervous system (CNS) with unique immune cell composition and routine CSF collection is integral for diagnosing various CNS disorders, offering a more practical alternative to assess the CNS. In this study, we described an end-to-end workflow to perform in-depth single-

…a decisive role in the pathology of neurodegenerative diseases, hence its relevance for investigation. Novel fMRI tools, e.g., the correlation between global grey matter (gGM) BOLD and CSF flow signal, have enabled neuroimaging researchers to study the system’s function. Yet, no studies are looking at whe

Metabolic disorders like diabetes and obesity markedly elevate the risk of neurodegenerative diseases. While certain medications used to manage these conditions show neuroprotective potential, their exact mechanisms of action remain elusive. Here, we propose the utilization of brain histology in a mouse prion model as an effective approach for drug screening in dementia and for exploring the cellular mechanisms of neuroprotection offered by anti-diabetic drugs. Our primary objective was to establish the morphological criteria for brain pathology in prion-infected mice. To achieve this, C57BL/6

…like Alzheimer’s and Parkinson’s diseases. While the role of neuromodulators in explicit learning is increasingly in the focus of the research, their participation in implicit learning and memory processes is poorly understood.To examine this we have used a previously developed automated training setup in which animals must respond to sequential light flashes at different locations. Following the

Cellular hallmarks of neurodegenerative diseases include loss of synapses, neuronal death, inflammation, energy homeostasis defects, oxidative stress, mitochondrial dysfunction, and aberrant proteostasis. AMP-activated kinase (AMPK) maintains energy homeostasis by responding to fluctuating ATP levels, with diverse targets ranging from changing the transcriptional program, promoting glucose uptake, inhibiting protein synthesis, inducing mitochondrial fission, mitophagy and autophagy. Evidence indicates that AMPK is hyperactivated in Alzheimer’s disease (AD), and amyloid-β (Aβ) can activate AMPK