Although there are numerous strategies to counteract the death of dopaminergic neurons in Parkinson’s disease (PD), there are currently no treatments that delay or prevent the disease course, indicating that early protective treatments are needed. Targeting axonal degeneration, a key initiating event in PD, is required to develop novel therapies; however, its underlying molecular mechanisms are not

Peripheral nerve injuries have the potential to bring about long-term disabilities in individuals. The major issue in repairing nerve injuries is the poor growth rate of axons. Although several molecules have been identified as potential candidates for improving axon growth, their potential translation into clinical practice is preliminary and largely unexplored. This necessitates identifying additional

Alzheimer's disease (AD) is a neurodegenerative disorder without a known cure or effective treatment. Research has identified several modifiable risk factors and suggested preventative measures to reduce the risk of developing AD, including alterations in diet. Polyunsaturated fatty acids (PUFAs) have been shown to regulate inflammatory responses in the central nervous system (CNS), the main site of

The importance of glial cells, mainly astrocytes, oligodendrocytes, and microglia, in the central nervous system (CNS) has been increasingly appreciated. Recent advances have demonstrated the diversity of glial cells and their contribution to human CNS development, normal CNS functions, and disease progression. The uniqueness of human glial cells is also supported by multiple lines of evidence. With

Alzheimer's disease (AD) is an age-related neurodegenerative disorder hallmarked by amyloid-β (Aβ) plaque accumulation, neuronal cell death, and cognitive deficits that worsen during disease progression. Histone acetylation dysregulation, caused by an imbalance between reduced histone acetyltransferases (HAT) Tip60 and increased histone deacetylase 2 (HDAC2) levels, can directly contribute to AD pathology

Dendritic spines are major sites of excitatory synaptic connection in pyramidal neurons of the forebrain, and their functional regulation underlies the development of functional neuronal circuits and experience-dependent circuit plasticity. Dendritic spines contain a large amount of actin filaments, and their organization and dynamics control both the morphology and function of dendritic spines. New

The immune system is crucial for normal neuronal development and function (neuroimmune system). Both immune and neuronal systems undergo significant postnatal development and are sensitive to developmental programming by environmental experiences. Negative experiences from infection to psychological stress at a range of different time points (in utero to adolescence) can permanently alter the function

Recent work demonstrated that sympathetic neurons innervate the skeletal muscle near the neuromuscular junction (NMJ), and muscle sympathectomy and sympathomimetic agents strongly influence motoneuron synaptic vesicle release ex vivo. Moreover, reports attest that the pontine nucleus locus coeruleus (LC) projects to preganglionic sympathetic neurons and regulates human mobility and skeletal muscle

Human SH-SY5Y neuroblastoma cells stably expressing exogenous CB1 (CB1XS) or CB2 (CB2XS) receptors were developed to investigate endocannabinoid signaling in the extension of neuronal projections. Expression of cannabinoid receptors did not alter proliferation rate, viability, or apoptosis relative to parental SH-SY5Y. Transcripts for endogenous cannabinoid system enzymes (diacylglycerol lipase, monoacylglycerol

Major depressive disorder (MDD) is one of the most prevalent stress-related mental disorders worldwide. Several biological mechanisms underlying the pathophysiology of MDD have been proposed, including endocrine disturbances, neurotransmitter deficits, impaired neuronal plasticity, and more recently, mitochondrial dysfunctions. In this review, we provide an overview of relevant molecular correlates

The incidence of Alzheimer’s disease (AD) is increasing with the aging population, and it has become one of the main health concerns of modern society. The dissection of the underlying pathogenic mechanisms and the development of effective therapies remain extremely challenging, also because available animal and cell culture models do not fully recapitulate the whole spectrum of pathological changes

Frontotemporal dementia (FTD) describes a group of clinically heterogeneous conditions that frequently affect people under the age of 65 (Le Ber et al., 2013). There are multiple genetic causes of FTD, including coding or splice-site mutations in MAPT, GRN mutations that lead to haploinsufficiency of progranulin protein, and a hexanucleotide GGGGCC repeat expansion in C9ORF72. Pathologically, FTD is

The current study sought to characterize the pro-survival effects of erythropoietin (EPO) in a toxicant model of Parkinson's disease (PD). EPO treatment induced time-dependent elevations of antioxidant glutathione peroxidase (GPx) and anti-apoptotic factors (pAkt and pBad/Bad) within the striatum and substantia nigra pars compacta (SNc). Intriguingly, our results indicated a region- and lesion size-

The studies of the interaction between the sympathetic and motor nervous systems are extremely relevant due to therapy for many neurodegenerative and cardiovascular disorders involving adrenergic compounds. Evidences indicate close contact between sympathetic varicosities and neuromuscular synapses. This raises questions about the effects of catecholamines on synaptic transmission. The currently available

The intrinsic necrosis of skeletal muscles in animal models of Duchenne muscular dystrophy (DMD) damages neuromuscular junctions (NMJs) with progressively altered NMJs associated with denervation and premature changes in dystrophic nerves. In the mdx mouse model of DMD, the proteins S100β and Tau5 are significantly increased in sciatic nerves by 13 months (M) of age, far earlier (by 9 M) than in normal

Astrocyte activation is one of the crucial hallmarks of Alzheimer's disease (AD) along with amyloid-β (Aβ) plaques, neurofibrillary tangles and neuron death. Glial scar and factors secreted from activated astrocytes have important contribution on neuronal health in AD. In this study, we investigated the mechanisms of astrocyte activation both in in vitro and in vivo models of AD. In this regard, mitogen

The Single Prolonged Stress protocol is considered a model for PTSD, as it induces long lasting changes in rat behaviour and endocrine regulation. Previous work demonstrated that some of these changes can be prevented by treatment with the glucocorticoid receptor antagonist RU486, administered a week after the stressor. The current study evaluated the effects of an earlier intervention with RU486,

Microglia are the resident innate immune cells of the central nervous system and exert functions of host defence and maintenance of normal tissue homeostasis, along with support of neuronal processes in the healthy brain. Chronic and dysregulated microglial cell activation has increasingly been linked to the status of neuroinflammation underlying many neurodegenerative diseases, including multiple

The extracellular accumulation of amyloid β (Aβ) fragments of amyloid precursor protein (APP) in brain parenchyma is a pathological hallmark of Alzheimer’s disease (AD). APP can be cleaved into Aβ on late endosomes/multivesicular bodies (MVBs). E3 ubiquitin ligases have been linked to Aβ production, but specific E3 ligases associated with APP ubiquitination that may affect targeting of APP to endosomes

Stressful and emotionally arousing experiences activate hormonal and brain systems that create strong memories. Extensive evidence indicates that this strengthening effect involves the synergistic action of both norepinephrine and glucocorticoid hormones. This tight regulation of emotional memories is normally highly adaptive and pivotal for survival; yet, aberrant memory processing of stressful events

Lysosomal storage diseases (LSDs) are a group of metabolism inborn errors caused by defective enzymes in the lysosome, resulting in the accumulation of undegraded substrates. Many characteristic cell features have been revealed in LSDs, including abnormal autophagy and mitochondrial dysfunction. The development of induced pluripotent stem cells (iPSCs) dramatically boosted research on LSDs, particularly

Epilepsy is among the most common neurological disorders, affecting approximately 50 million people worldwide. Importantly, epilepsy is genetically and etiologically heterogenous, but several epilepsy types exhibit similar clinical presentations. Epilepsy-associated genes are being identified. However, the molecular pathomechanisms remain largely unknown. Approximately one-third of epilepsy is refractory

Mutations affecting SQSTM1 coding for p62 and TANK-Binding Kinase 1 (TBK1) have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TBK1 is a serine-threonine kinase that regulates p62's activity as an autophagy receptor via phosphorylation and also has roles in neuroinflammatory signalling pathways. The mechanisms underlying ALS and FTLD pathogenesis

Peroxisomes exist in nearly every cell, oxidizing fats, synthesizing lipids and maintaining redox balance. As the brain ages, multiple pathways are negatively affected, but it is currently unknown if peroxisomal proteins are affected by aging in the brain. While recent studies have investigated a PEX5 homolog in aging C. elegans models and found that it is reduced in aging, it is unclear if PEX5, a

Neurotrauma is among main causes of human disability and death. We studied effects of axotomy on ultrastructure and neuronal activity of a simple model object – an isolated crayfish stretch receptor that consists of single mechanoreceptor neurons (MRN) enwrapped by multilayer glial envelope. After isolation, MRN regularly fired until spontaneous activity cessation. Axotomy did not change significantly

The blood-brain barrier (BBB) constitutes the interface between the blood and the brain tissue. Its primary function is to maintain the tightly controlled microenvironment of the brain. Models of the BBB are useful for studying the development and maintenance of the BBB as well as diseases affecting it. Furthermore, BBB models are important tools in drug development and support the evaluation of the

Neuropsychiatric disorders are highly heritable polygenic disorders arising from the complex interplay of highly penetrant rare variants and common variants of small effect. There is a large index of comorbidity and shared genetic risk between disorders, reflecting the pleiotropy of individual variants as well as predicted downstream pathway-level convergence. Importantly, the mechanism(s) through

The cerebellum is a brain region located in the dorsal part of the anterior hindbrain, composed of a highly stereotyped neural circuit structure with small sets of neurons. The cerebellum is involved in a wide variety of functions such as motor control, learning, cognition and others. Damage to the cerebellum often leads to impairments in motor skills (cerebellar ataxia). Cerebellar ataxia can occur

Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP) are retinal degenerative disorders that dramatically damage the retina. As there is no therapeutic option for the majority of patients, vision is progressively and irremediably lost. Owing to their unlimited renewal and potency to give rise to any cell type of the human adult body, human pluripotent stem cells (hPSCs) have been extensively

Vision loss has long since been considered irreversible after a critical period; however, there is potential to restore limited vision, even in adulthood. This phenomenon is particularly pronounced following complete loss of vision in the dominant eye. Adult neural cell adhesion molecule (NCAM) knockout mice have an age-related impairment of visual acuity. The underlying cause of early deterioration

Multiple C2 and Transmembrane Domain Proteins (MCTPs) are putative calcium sensors. Proteins that contain C2 domains play essential roles in membrane trafficking and exocytosis; however, MCTPs functions in neurotransmitter release are not known. Here we report that in C. elegans mctp-1 is under the control of two promoters - one active in the nervous system and the second in the spermatheca. We generated

Neurons are highly polarized cells that have specialized regions for synaptic input, the dendrites, and synaptic output, the axons. This polarity is critical for appropriate neural circuit formation and function. One of the central gaps in our knowledge is understanding how developing neurons initiate axon polarity. Given the critical nature of this polarity on neural circuit formation and function

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily targets motor neurons. Motor neurons from ALS patients show cytoplasmic inclusions that are reflective of an altered RNA metabolism and protein degradation. Causal gene mutations are found in all cell types even though patient motor neurons are by far the most susceptible to the degeneration. Using induced pluripotent

The brain is exceptionally demanding in terms of energy metabolism. Approximately 20% of the calories consumed are devoted to our cerebral faculties, with the lion's share provided in the form of glucose. The brain's stringent energy dependency requires a high degree of harmonization between the elements responsible for supplying- and metabolizing energetic substrates. However, chronic stress may jeopardize

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid with strong neuroprotective properties that is important for normal excitability and synaptic transmission in the hippocampal neurons. Considering the above, the aim of the present study was to determine whether increasing brain S1P level is able to reverse spatial memory impairment in streptozotocin-diabetic rats. The experiment was carried

Cell polarity is defined as the asymmetric distribution of cellular components along an axis. Most cells, from the simplest single-cell organisms to highly specialized mammalian cells, are polarized and use similar mechanisms to generate and maintain polarity. Cell polarity is important for cells to migrate, form tissues, and coordinate activities. During development of the mammalian cerebral cortex

Tcf4 has been linked to autism, schizophrenia, and Pitt-Hopkins Syndrome (PTHS) in humans, suggesting a role for Tcf4 in brain development and importantly cortical development. However, the mechanisms behind its role in disease and brain development are still elusive. We provide evidence that Tcf4 has a critical function in the differentiation of cortical regions, corpus callosum and anterior commissure

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the midbrain. In recent years, researchers have started studying PD using induced pluripotent stem cell (iPSC) models of the disease. Surprisingly, few studies have combined iPSC-technology with the so-called powerful 'omics' approaches. Here, we review the current state of omics applications

Normal development of neuronal connections in the hippocampus requires neurotrophic signals, including the cytokine leptin. During neonatal development, leptin induces formation and maturation of dendritic spines, the main sites of glutamatergic synapses in the hippocampal neurons. However, the molecular mechanisms for leptin-induced synaptogenesis are not entirely understood. In this study, we reveal

Platinum-based chemotherapeutics still play an important role in cancer therapy, however, severe side effects, such as painful neuropathy, occur frequently. The pathophysiologic mechanisms depend on the applied chemotherapeutic agent and are still controversial. In addition to neuronal damage, disturbance of glial cell activity may contribute to neurotoxicity. Here, we focused on the effect of oxaliplatin

The BRICHOS domain is found in human precursor proteins associated with cancer, dementia (Bri2) and amyloid lung disease (proSP-C). Recombinant human (rh) proSP-C and Bri2 BRICHOS domains delay amyloid-β peptide (Aβ) fibril formation and reduce associated toxicity in vitro and their overexpression reduces Aβ neurotoxicity in animal models of Alzheimer's disease. After intravenous administration in

Various animal models have been employed to understand the pathogenic mechanism of neuropathic pain. Nitric oxide (NO) is an important molecule in nociceptive transmission and is involved in neuropathic pain. However, its mechanistic actions remain unclear. The aim of this study was to better understand the involvement of neuronal and inducible isoforms of nitric oxide synthase (nNOS and iNOS) in neuropathic

Neuroinflammation contributes to neurodegenerative disorders, including Alzheimer's disease (AD). Gut microbes are involved in regulating systemic inflammation. Short-chain fatty acids (SCFAs), which are among the many metabolites released by gut microbes, can cross the blood-brain barrier (BBB) and interact with microglia. High concentrations of individual SCFAs decrease the inflammatory responses

Potassium K2P ('leak') channels conduct current across the entire physiological voltage range and carry leak or 'background' currents that are, in part, time- and voltage-independent. K2P2.1 channels (i.e., TREK-1, KCNK2) are highly expressed in excitable tissues, where they play a key role in the cellular mechanisms of neuroprotection, anesthesia, pain perception, and depression. Here, we report for

The vomeronasal organ (VNO), the sensory organ of the mammalian accessory olfactory system, mediates the activation of sexually dimorphic reproductive behavioral and endocrine responses in males and females. It is unclear how sexually dimorphic and state-dependent responses are generated by vomeronasal sensory neurons (VSNs). Here, we report the expression of the transient receptor potential (TRP)

Neuronal dendrites are highly branched and specialized compartments with distinct structures and secretory organelles (e.g., spines, Golgi outposts), and a unique cytoskeletal organization that includes microtubules of mixed polarity. Dendritic membranes are enriched with proteins, which specialize in the formation and function of the post-synaptic membrane of the neuronal synapse. How these proteins

This study investigates changes with respect to increasing protein levels in dystrophic nerves of two mdx mouse models of Duchenne muscular dystrophy (DMD). We propose that these nerve changes result from progressive ongoing damage to neuromuscular junctions (NMJs) due to repeated intrinsic bouts of necrosis in dystrophic muscles. We compared sciatic nerves from classic mdx mice aged 13, 15 and 18 months

Acetylcholinergic (ACh) neurotransmission is essential for key organismal functions such as locomotion and cognition. However, the mechanism through which ACh is regulated in the central nervous system is not fully understood. The vesicular acetylcholine transporter (VAChT) mediates the packaging and transport of ACh for exocytotic release and is a critical component of the ACh release machinery. Yet

Dystrophin deficiency is associated with alterations in cell physiology. The functional consequences of dystrophin deficiency are particularly severe for muscle physiology, as observed in Duchenne muscle dystrophy (DMD). DMD is caused by the absence of a 427 kDa isoform of dystrophin. However, in addition to muscular dystrophy symptoms, DMD is frequently associated with memory and attention deficits

The development of the cerebral cortex depends on numerous parameters, including extracellular cues and microenvironmental factors that also affect gene expression. C-Terminal Binding Proteins (CtBPs) 1 and 2 are transcriptional co-repressors which have been shown to be critically involved in embryonic development. CtBPs are oxygen sensing molecules, and we have previously demonstrated an important

The perception of odors relies on combinatorial codes consisting of odorant receptor (OR) response patterns to encode odor identity. Modulation of these patterns by odorant interactions at ORs potentially explains several olfactory phenomena: mixture suppression, unpredictable sensory outcomes, and the perception of odorant mixtures as unique objects. We determined OR response patterns to 4 odorants

The zebrafish pineal organ is a photoreceptive structure containing two main neuronal populations (photoreceptors and projections neurons). Here we describe a subpopulation of projection neurons that expresses the melanopsin gene, opn4xa. This new pineal cell type, that displays characteristics of both projection neurons and photoreceptors, share a similar dependency for BMP and Notch signalling pathways

Neurons are polarized cells, with dendrites and axons that require different complements of membrane proteins to fulfill their specialized functions. Membrane proteins are synthesized in the somatodendritic domain and delivered to their target membranes via long-range vesicle transport. Most anterograde vesicle transport is mediated by kinesin motors, but it is unclear how kinesins are targeted to

Intracellular accumulation of amyloid-β protein (Aβ) is an early event in Alzheimer's disease (AD). The autophagy-lysosomal pathway is an important pathway for maintaining cellular proteostasis and for the removal of damaged organelles and protein aggregates in all eukaryotes. Despite mounting evidence showing that modulating autophagy promotes clearance of Aβ aggregates, the regulatory mechanisms