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Category: neuroscience – Page 3

Role of ubiquilin-2 liquid droplets in α-synuclein aggregation

Parkinson’s disease (PD) is an age-related, progressive neurodegenerative disorder. The hallmark of PD pathogenesis is the Lewy bodies (LBs) that accumulate in neurons in the substantia nigra region of the brain, damaging these neurons and leading to the motor symptoms of the disease. α-synuclein (α-syn), a misfolded protein, aggregates and forms fibrils, which leads to the formation of LBs. The exact molecular mechanism behind this aggregation process is yet to be uncovered. With an increasing number of elderly patients suffering from Parkinson’s and other neurodegenerative diseases worldwide, it is important to understand the aggregation process, find potential therapeutic targets to mitigate or inhibit the aggregation, and slow down the disease progression.

Liquid-liquid phase separation (LLPS), a process where a uniform mixture spontaneously divides into two liquid phases with differing component concentrations, is often considered the reason behind α-syn aggregation. Even though LLPS of α-syn was previously reported, the question remains: are they involved in catalyzing the early stage of aggregation? Ubiquilin-2 (UBQLN2) protein, mainly involved in maintaining protein homeostasis, also undergoes LLPS under certain physiological conditions. Interestingly, it is known to be associated with several neurodegenerative diseases.

Are liquid droplets formed by UBQLN2 catalyzing the α-syn protein aggregation? A team of researchers decided to unravel the involvement of UBQLN2 in α-syn aggregation and fibril formation. “By uncovering the mechanisms that trigger the aggregation process, we hope to find new ways to prevent it and ultimately contribute to the development of disease-modifying treatments,” mentioned the senior author of the study. The study was published in The EMBO Journal.

Scientists Uncover How Tiny “Nanopores” Learn Like the Brain

Scientists found that nanopores’ electrical charges control how ions flow and when pores temporarily shut down. The discovery could allow engineers to design nanopores that “learn” like synapses for next-generation computing.

Pore-forming proteins appear across many forms of life. In humans, they help protect the body by supporting immune defenses. In bacteria, they often function as toxins that create openings in cell membranes. These natural pores regulate the movement of ions and molecules, and their precise control over molecular transport has made them valuable in biotechnology, including DNA sequencing and molecular sensing.

Unpredictable Behavior in Ion Flow.

Plant hormone allows lifelong control of proteins in living animal for first time

Researchers have found a way to control protein levels inside different tissues of a whole, living animal for the first time. The method lets scientists dial protein levels up or down with great precision during the animal’s entire life, a technological advance which can help them study the molecular underpinnings of aging and disease.

Scientists at the Center for Genomic Regulation in Barcelona and the University of Cambridge successfully tested the technique by controlling how much protein was present in the intestines and neurons of the nematode worm Caenorhabditis elegans. Their findings are described in the journal Nature Communications.

Dr. Norman Putzki, MD — Novartis — Gene Therapy And A New Era Of Neuroscience

Gene Therapy And A New Era Of Neuroscience — Dr. Norman Putzki, MD — SVP, Global Clinical Development Head, and U.S. Development Site Head, Novartis.

Dr. Norman Putzki, MD is Senior Vice President, Global Clinical Development Head, and U.S. Development Site Head at Novartis (https://www.novartis.com/) where he oversees global teams working on next-generation gene therapies, RNA-based medicines, targeted biologics, and innovative small molecules.

Dr. Putzki most recently served as Global Head of Development for Neuroscience and Gene Therapy at Novartis, where he oversaw one of the world’s most ambitious pipelines aimed at transforming the lives of patients with neurological, neuromuscular, and rare genetic diseases.

A physician–scientist by training, with an MD from University of Duisburg Essen, Dr. Putzki has built a career at the intersection of clinical medicine, translational research, and large-scale drug development.

Before joining Novartis, Dr. Putzki led programs across multiple therapeutic areas at Biogen Idec and has played key roles in advancing clinical treatments for conditions long considered intractable including MS and Parkison’s disease.

Continue reading “Dr. Norman Putzki, MD — Novartis — Gene Therapy And A New Era Of Neuroscience” | >

Study reveals visual processing differences in dyslexia extend beyond reading

New research published in Neuropsychologia provides evidence that adults with dyslexia process visual information differently than typical readers, even when viewing non-text objects. The findings suggest that the neural mechanisms responsible for distinguishing between specific items, such as individual faces or houses, are less active in the dyslexic brain. This implies that dyslexia may involve broader visual processing differences beyond the well-known difficulties with connecting sounds to language.

Dyslexia is a developmental condition characterized by significant challenges in learning to read and spell. These difficulties persist despite adequate intelligence, sensory abilities, and educational opportunities. The most prominent theory regarding the cause of dyslexia focuses on a phonological deficit. This theory posits that the primary struggle lies in processing the sounds of spoken language.

According to this view, the brain struggles to break words down into their component sounds. This makes mapping those sounds to written letters an arduous task. However, reading is also an intensely visual activity. The reader must rapidly identify complex, fine-grained visual patterns to distinguish one letter from another.

From mind-controlling tech to clinical therapy

Researchers at the University of Geneva, together with colleagues in Switzerland, France, the United States and Israel, describe how optogenetic control of brain cells and circuits is already steering both indirect neuromodulatory therapies and first-in-human retinal interventions for blindness, while sketching the practical and ethical conditions needed for wider clinical use.

Optogenetic control uses light to impose temporally precise gain or loss of function in specific cell types, or even individual cells. Selected by location, connections, gene expression or combinations of these features, researchers now have an unprecedented way to investigate the brain within living animals.

Modern experiments range from implanted fiber optics to three-dimensional holographic illumination of defined neuronal ensembles and noninvasive wearable LEDs, with interventions that can run from milliseconds to chronic use and effect sizes that change rapidly with changes in light intensity.

A prospective study of minimally invasive keyhole craniotomy and stereotactic brachytherapy for new brain oligometastases

Mahapatra et al. show how minimally invasive keyhole craniotomy combined with brachytherapy provides strong local control for brain metastases, with no radiation necrosis and improved neurological and cognitive outcomes, highlighting this approach as a promising alternative to WBRT and SRS. JNOO

Read more here.

Metastatic brain tumors (MBTs) are the most common intracranial tumors, affecting up to 40% of cancer patients. Traditional treatments such as Whole Brain Radiotherapy (WBRT) and Stereotactic Radiosurgery (SRS) have limitations, including neurocognitive decline and potential tumor regrowth. Minimally invasive keyhole craniotomy (MIKC) and Cesium-131 (Cs-131) brachytherapy offer promising alternatives due to their precision and reduced side effects. This prospective study aims to evaluate the safety and efficacy of combining MIKC with Cs-131 brachytherapy in treating newly diagnosed brain oligometastases.

Twenty-one adults with newly diagnosed brain metastases were enrolled from 2019 to 2021. Preoperative T1 MRI with gadolinium was used to calculate the gross tumor volume (GTV). Minimally invasive craniotomies were performed with resection of these tumors, followed by the implantation of Cs-131 seeds. Postoperative imaging was conducted to verify seed placement and resection. Dosimetric values (V100, V200, D90) were calculated. Patients were followed every two months for two years to monitor local progression, functional outcomes, and quality of life. The primary endpoint was freedom from local progression, with secondary endpoints including overall survival, functional outcomes, quality of life, and treatment-related complications.

The median preoperative tumor volume was 10.65 cm3, reducing to a resection cavity volume of 6.05 cm3 post-operatively. Dosimetric analysis showed a median V100 coverage of 93.2%, V200 of 43.9%, and D90 of 89.8 Gy. The 1-year local freedom from progression (FFP) was 91.67%, while the distant FFP was 53.91%. Five patients remained alive at the study’s end, with a median survival duration of 5.9 months, a duration likely impacted by the concurrent COVID-19 pandemic. Only one patient experienced local recurrence, and no cases of radiation necrosis were observed. Significant improvements were seen in neurological, functional, and cognitive symptoms.

Molecular basis for de novo thymus regeneration in a vertebrate, the axolotl

In humans, the loss of thymic function through thymectomy, environmental challenges, or age-dependent involution is associated with increased mortality, inflammaging, and higher risk of cancer and autoimmune disease (1). This is largely due to a decline in the intrathymic naïve T cell pool, whose generation is orchestrated by the thymic stroma, particularly thymic epithelial cells (TECs) (2). Upon challenges that affect the TEC compartment, the thymus is capable of triggering an endogenous regenerative response by engaging resident epithelial progenitors with stem cell features (3–5). Yet, after age-related atrophy or thymectomy resulting from myasthenia gravis or tumor removal (1), this regenerative response is unable to overcome the loss of thymic tissue, highlighting the need for therapeutic interventions.

The restoration of thymic functionality has been achieved to a limited extent via strategies targeting the thymic epithelial microenvironment or hematopoietic progenitors, modulating hormones and metabolism, or through cellular therapies and bioengineering (6). In mice, the up-regulation of Foxn1, a key transcription factor for thymus development and organogenesis (7), either directly or via its upstream effector bone morphogenetic protein 4 (BMP4), can support activity of cortical TECs (cTECs) (8, 9). Further, a combination of growth hormone and metformin has been shown to restore thymic functional mass in humans (10). Nevertheless, such strategies only lead to delayed thymic involution, and examples of complete thymus regeneration have not yet been described among vertebrates.

Because of its remarkable regenerative abilities that extend to parts of the brain, eye, heart, and spinal cord, and even entire limbs, the axolotl (Ambystoma mexicanum) is a powerful model for regeneration studies (11). The axolotl has offered insights into the mechanisms of positional identity (12), cell plasticity (13, 14), and the molecular basis of complex regeneration (15–18). The regeneration of axolotl body parts relies on remnants of the missing structure, with the exception of lens tissue, which can regrow from dorsal pigmented epithelial cells during a short window during development (19). However, whether de novo regeneration can occur for an entire complex organ, in axolotls or any other vertebrate, is unknown.

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