Disrupting the interaction between AMBRA1 and DLC1 prevents apoptosis while enhancing autophagy and mitophagy.

AMBRA1 has critical roles in autophagy, mitophagy, cell cycle regulation, neurogenesis and apoptosis. Dysregulation of these processes are hallmarks of various neurodegenerative diseases and therefore AMBRA1 represents a potential therapeutic target. The flexibility of its intrinsically disordered regions allows AMBRA1 to undergo conformational changes and thus to perform its function as an adaptor protein for various different complexes.

Three-Dimensional Bioprinting of Human iPSC-Derived Neuron-Astrocyte Cocultures for Screening Applications.

For a cell model to be viable for drug screening, the system must meet throughput and homogeneity requirements alongside having an efficient development time. However, many published 3D models do not satisfy these criteria. This therefore, limits their usefulness in early drug discovery applications.

Inhibition of insulin-degrading enzyme in human neurons promotes amyloid-β deposition.

Alzheimer's disease (AD) is characterised by the aggregation and deposition of amyloid-β (Aβ) peptides in the human brain. In age-related late-onset AD, deficient degradation and clearance, rather than enhanced production, of Aβ contributes to disease pathology. In the present study, we assessed the contribution of the two key Aβ-degrading zinc metalloproteases, insulin-degrading enzyme (IDE) and neprilysin (NEP), to Aβ degradation in human induced pluripotent stem cell (iPSC)-derived cortical neurons.

Children's knowledge and feelings align in response to emotional music.

Examining emotion recognition and response to music can isolate recognition of and resonance with emotion from the confounding effects of other social cues (e.g., faces).

"But not the music": psychopathic traits and difficulties recognising and resonating with the emotion in music.

Recognising and responding appropriately to emotions is critical to adaptive psychological functioning. Psychopathic traits (e.g.

3D models of neurodegeneration: implementation in drug discovery.

A lack of in vitro models that robustly represent the complex cellular pathologies underlying neurodegeneration has resulted in a translational gap between in vitro and in vivo results, creating a bottleneck in the development of new therapeutics. In the past decade, new and complex 3D models of the brain have been published at an exponential rate. However, many novel 3D models of neurodegeneration overlook the validation and throughput requirements for implementation in drug discovery.

Are you laughing with me or at me? Psychopathic traits and the ability to distinguish between affiliation and dominance laughter cues.

Objective: Laughter conveys important information that supports social communication and bonding. Research suggests that unique acoustic properties distinguish laughter that promotes affiliation from laughter that conveys dominance, but little is known about potential individual differences in laughter interpretation or contagion based on these specified social functions of laughter. Psychopathy is associated with both affiliative deficits (e.

A Validation Study of the BRIEF-2 Among Kindergarteners and First Graders At-Risk for Behavior Problems.

Early identification of executive dysfunction and timely school-based intervention efforts are critical for students at risk for problematic behaviors during early elementary school. The original Behavior Rating Inventory of Executive Functioning (BRIEF) was designed to measure real-world behavioral manifestations of executive functioning, neurocognitive processes critical for school success. With the updated BRIEF-2, independent validation is needed with kindergarten and first grade students at risk for emotional and behavioral disorders.

Efficacy of the social-emotional learning foundations curriculum for kindergarten and first grade students at risk for emotional and behavioral disorders.

Researchers have shown that children's social-emotional growth is inextricably connected to academic learning. We developed the Social-Emotional Learning Foundations (SELF) intervention, a Grade K-1 curriculum merging social-emotional learning (SEL) and literacy instruction, to promote language supported self-regulation, specifically for primary grade children at early risk for emotional or behavioral difficulties. We report findings from a pretest-posttest cluster randomized efficacy trial with one fixed between-subjects factor to test the effects of teacher-delivered SEL instruction against those of business as usual (BAU).

Cognitive aging is associated with redistribution of synaptic weights in the hippocampus.

Behaviors that rely on the hippocampus are particularly susceptible to chronological aging, with many aged animals (including humans) maintaining cognition at a young adult-like level, but many others the same age showing marked impairments. It is unclear whether the ability to maintain cognition over time is attributable to brain maintenance, sufficient cognitive reserve, compensatory changes in network function, or some combination thereof. While network dysfunction within the hippocampal circuit of aged, learning-impaired animals is well-documented, its neurobiological substrates remain elusive.

The Impact of the COVID-19 Pandemic on Children's Conduct Problems and Callous-Unemotional Traits.

The COVID-19 pandemic has dramatically altered family life, but whether family exposures to and worries about the COVID-19 pandemic has impacted child conduct problems (CP) and callous-unemotional (CU) traits is unknown. Thus, we evaluated 303 parents (M = 38.04; SD = 5.

Reduced sensitivity to affiliation and psychopathic traits.

Psychopathy is characterized by affective and interpersonal deficits, deviant lifestyle, and antisocial behaviors. Much research has been dedicated to understanding the impairments in reinforcement learning, fear conditioning, and sensitivity to threat, distress, or fear in others, which are thought to underpin psychopathic traits. Fewer studies have examined deficits in affiliative processes, which could provide insight into mechanisms giving rise to the impairments in social bonding, closeness with others, and cooperation that also characterize individuals high on psychopathy.

Blended alginate/collagen hydrogels promote neurogenesis and neuronal maturation.

Brain extracellular matrix (ECM) is complex, heterogeneous and often poorly replicated in traditional 2D cell culture systems. The development of more physiologically relevant 3D cell models capable of emulating the native ECM is of paramount importance for the study of human induced pluripotent stem cell (iPSC)-derived neurons. Due to its structural similarity with hyaluronic acid, a primary component of brain ECM, alginate is a potential biomaterial for 3D cell culture systems.

Proteolytic shedding of the prion protein via activation of metallopeptidase ADAM10 reduces cellular binding and toxicity of amyloid-β oligomers.

The cellular prion protein (PrP) is a key neuronal receptor for β-amyloid oligomers (AβO), mediating their neurotoxicity, which contributes to the neurodegeneration in Alzheimer's disease (AD). Similarly to the amyloid precursor protein (APP), PrP is proteolytically cleaved from the cell surface by a disintegrin and metalloprotease, ADAM10. We hypothesized that ADAM10-modulated PrP shedding would alter the cellular binding and cytotoxicity of AβO.

Soluble Amyloid Precursor Protein α: Friend or Foe?

The "amyloidogenic" proteolytic processing of the cell surface amyloid precursor protein (APP) produces amyloid-β, which causes a range of detrimental effects in the neuron, such as synaptic loss, and plays a key role in Alzheimer's disease. In contrast, "non-amyloidogenic" proteolytic processing, which involves the cleavage of APP by α-secretase, produces soluble amyloid precursor protein α (sAPPα) and is the most predominant proteolytic processing of APP in the healthy brain. Current research suggests that sAPPα plays a role in synaptic growth and plasticity, but whether this role is protective or detrimental is age-dependent.

Store depletion-induced h-channel plasticity rescues a channelopathy linked to Alzheimer's disease.

Voltage-gated ion channels are critical for neuronal integration. Some of these channels, however, are misregulated in several neurological disorders, causing both gain- and loss-of-function channelopathies in neurons. Using several transgenic mouse models of Alzheimer's disease (AD), we find that sub-threshold voltage signals strongly influenced by hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels progressively deteriorate over chronological aging in hippocampal CA1 pyramidal neurons.

Tau Proteolysis in the Pathogenesis of Tauopathies: Neurotoxic Fragments and Novel Biomarkers.

With predictions showing that 131.5 million people worldwide will be living with dementia by 2050, an understanding of the molecular mechanisms underpinning disease is crucial in the hunt for novel therapeutics and for biomarkers to detect disease early and/or monitor disease progression. The metabolism of the microtubule-associated protein tau is altered in different dementias, the so-called tauopathies.

Identification of TMEM230 mutations in familial Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative disorder without effective treatment. It is generally sporadic with unknown etiology. However, genetic studies of rare familial forms have led to the identification of mutations in several genes, which are linked to typical Parkinson's disease or parkinsonian disorders.

Telomere length in bipolar disorder and lithium response.

Telomeres consist of exanucleotide tandem repeats and proteins complexes at the end of chromosome ends. Telomeres shorten at each cell division, and as such telomere length is a marker of cellular age. Accelerated telomere shortening and cell senescence have been associated with a number of chronic medical conditions, including psychiatric disorders, where increased prevalence of age-related disorders and shorter telomere length have been reported.