Abstract:
:Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease affecting both upper and lower motor neurons. The molecular mechanisms underlying disease pathogenesis remain largely unknown. Multiple genetic loci including genes involved in proteostasis and ribostasis have been linked to ALS providing key insights into the molecular mechanisms underlying disease. In particular, the identification of the RNA binding proteins TDP-43 and fused in sarcoma (FUS) as causative factors of ALS resulted in a paradigm shift centered on the study of RNA dysregulation as a major mechanism of disease. With wild-type TDP-43 pathology being found in ~97% of ALS cases and the identification of disease causing mutations within its sequence, TDP-43 has emerged as a prominent player in ALS. More recently, studies of the newly discovered C9orf72 repeat expansion are lending further support to the notion of defects in RNA metabolism as a key factor underlying ALS. RNA binding proteins are involved in all aspects of RNA metabolism ranging from splicing, transcription, transport, storage into RNA/protein granules, and translation. How these processes are affected by disease-associated mutations is just beginning to be understood. Considerable work has gone into the identification of splicing and transcription defects resulting from mutations in RNA binding proteins associated with disease. More recently, defects in RNA transport and translation have been shown to be involved in the pathomechanism of ALS. A central hypothesis in the field is that disease causing mutations lead to the persistence of RNA/protein complexes known as stress granules. Under times of prolonged cellular stress these granules sequester specific mRNAs preventing them from translation, and are thought to evolve into pathological aggregates. Here we will review recent efforts directed at understanding how altered RNA metabolism contributes to ALS pathogenesis.
journal_name
Front Cell Neuroscijournal_title
Frontiers in cellular neuroscienceauthors
Coyne AN,Zaepfel BL,Zarnescu DCdoi
10.3389/fncel.2017.00243subject
Has Abstractpub_date
2017-08-17 00:00:00pages
243issn
1662-5102journal_volume
11pub_type
杂志文章,评审abstract::Microglial activation is a key pathogenic process at the onset of Alzheimer's disease (AD). Identifying regulators of microglial activation bears great potential in elucidating causes and mechanisms of AD and determining candidates for early intervention. Previous studies demonstrate abnormal elevation of glutaminase ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00264
更新日期:2019-06-28 00:00:00
abstract::IN ADULT MAMMALS, UNDER PHYSIOLOGICAL CONDITIONS, NEUROGENESIS, THE PROCESS OF GENERATING NEW FUNCTIONAL NEURONS FROM PRECURSOR CELLS, OCCURS MAINLY IN TWO BRAIN AREAS: the subgranular zone in the dentate gyrus of the hippocampus, and the subventricular zone (SVZ) lining the walls of the brain lateral ventricles. Taki...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2012.00034
更新日期:2012-08-09 00:00:00
abstract::Besides its "classical" neurotransmitter function, serotonin (5-HT) has been found to also act as a neurodevelopmental signal. During development, the 5-HT projection system, besides an external placental source, represents one of the earliest neurotransmitter systems to innervate the brain. One of the targets of the ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2013.00143
更新日期:2013-10-04 00:00:00
abstract::Intermittent fasting (IF) was suggested to be a powerful nutritional strategy to prevent the onset of age-related neurodegenerative diseases associated with compromised brain bioenergetics. Whether the application of IF in combination with a mitochondrial insult could buffer the neurodegenerative process has never bee...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00004
更新日期:2018-01-17 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two progressive, fatal neurodegenerative syndromes with considerable clinical, genetic and pathological overlap. Clinical symptoms of FTD can be seen in ALS patients and vice versa. Recent genetic discoveries conclusively link the two diseases, ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00414
更新日期:2015-10-27 00:00:00
abstract::Type III adenylyl cyclase (AC3, ADCY3) is predominantly enriched in neuronal primary cilia throughout the central nervous system (CNS). Genome-wide association studies in humans have associated ADCY3 with major depressive disorder and autistic spectrum disorder, both of which exhibit sexual dimorphism. To date, it is ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00034
更新日期:2019-02-13 00:00:00
abstract::Behavioral and electrophysiological studies of Alzheimer's disease (AD) and other tauopathies have revealed that the onset of cognitive decline correlates better with synaptic dysfunctions than with hallmark pathologies such as extracellular amyloid-β plaques, intracellular hyperphosphorylated tau or neuronal loss. Re...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00034
更新日期:2014-02-10 00:00:00
abstract::P2X receptor channels mediate fast excitatory signaling by ATP and play major roles in sensory transduction, neuro-immune communication and inflammatory response. P2X receptors constitute a gene family of calcium-permeable ATP-gated cation channels therefore the regulation of P2X signaling is critical for both membran...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2013.00226
更新日期:2013-11-25 00:00:00
abstract::Secreted amyloid precursor protein-alpha (sAPPα), generated by enzymatic processing of the APP, possesses a range of neurotrophic and neuroprotective properties and plays a critical role in the molecular mechanisms of memory and learning. One of the key active regions of sAPPα is the central APP domain (E2) that conta...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00459
更新日期:2019-10-18 00:00:00
abstract::Maturation of neuronal and synaptic functions during early life is essential for the development of neuronal circuits and behaviors. In newborns synaptic transmission at excitatory synapses is primarily mediated by N-methyl-D-aspartate receptors (NMDARs), and NMDAR-mediated signaling plays an important role in synapti...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2017.00353
更新日期:2017-11-07 00:00:00
abstract::Intensity and frequency are the two main properties of sound. The non-monotonic neurons in the auditory system are thought to represent sound intensity. The central nucleus of the inferior colliculus (ICC), as an important information integration nucleus of the auditory system, is also involved in the processing of in...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00131
更新日期:2019-04-04 00:00:00
abstract::The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizin...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00047
更新日期:2015-02-24 00:00:00
abstract::The inferior olive (IO) is a nucleus located in the brainstem and it is part of the olivo-cerebellar loop. This circuit plays a fundamental role in generation and acquisition of coherent motor patterns and it relies on synchronous activation of groups of Purkinje cells (PC) in the cerebellar cortex. IO neurons integra...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2017.00397
更新日期:2017-12-14 00:00:00
abstract::A major challenge in the development of pharmacotherapies for autism is the failure to identify pathophysiological mechanisms that could be targetable. The majority of developing strategies mainly aim at restoring the brain excitatory/inhibitory imbalance described in autism, by targeting glutamate or GABA receptors. ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2020.588662
更新日期:2020-10-30 00:00:00
abstract::Despite a century of intensive investigation the effective treatment of protein aggregation diseases remains elusive. Ordinarily, molecular chaperones ensure that proteins maintain their functional conformation. The appearance of misfolded proteins that aggregate implies the collapse of the cellular chaperone quality ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2014.00191
更新日期:2014-07-08 00:00:00
abstract::Autism spectrum disorder (ASD) is a neurodevelopmental disorder that lacks clear biological biomarkers. Existing diagnostic methods focus on behavioral and performance characteristics, which complicates the diagnosis of patients younger than 3 years-old. The purpose of this study is to characterize metabolic features ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00150
更新日期:2019-04-30 00:00:00
abstract::Neuronal synchronization at gamma band frequency (20-80 Hz, γ oscillations) is closely associated with higher brain function, such as learning, memory and attention. Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the hippocampus, and modulate hippocampal γ oscillations, but the intracellular mechan...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2017.00057
更新日期:2017-03-06 00:00:00
abstract::Gastrointestinal (GI) pain is a common clinical problem, for which effective therapy is quite limited. Sensations from the GI tract, including pain, are mediated largely by neurons in the dorsal root ganglia (DRG), and to a smaller extent by vagal afferents emerging from neurons in the nodose/jugular ganglia. Neurons ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00412
更新日期:2015-10-13 00:00:00
abstract::Early odor preference learning in rodents occurs within a sensitive period [≤postnatal day (P)10-12], during which pups show a heightened ability to form an odor preference when a novel odor is paired with a tactile stimulation (e.g., stroking). Norepinephrine (NE) release from the locus coeruleus during stroking medi...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00450
更新日期:2015-11-19 00:00:00
abstract::After damage, axons in the peripheral nervous system (PNS) regenerate and regrow following a process termed Wallerian degeneration, but the regenerative process is often incomplete and usually the system does not reach full recovery. Key steps to the creation of a permissive environment for axonal regrowth are the tra...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2019.00093
更新日期:2019-03-20 00:00:00
abstract::Magnocellular neurons in the supraoptic nucleus (SON), which synthesize and release arginine vasopressin (AVP) and oxytocin (OT), express several subtypes of ATP-stimulated purinergic P2X receptors (P2XR) that modulate neuronal activity as well as neurotransmitter and hormone release. However, the physiological impact...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00284
更新日期:2019-06-26 00:00:00
abstract::Neurodegenerative diseases in general and specifically late-onset Alzheimer's disease (LOAD) involve a genetically complex and largely obscure ensemble of causative and risk factors accompanied by complex feedback responses. The advent of "high-throughput" transcriptome investigation technologies such as microarray an...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00089
更新日期:2014-03-27 00:00:00
abstract::Anoxic depolarization (AD) is a hallmark of ischemic brain damage. AD is associated with a spreading wave of neuronal depolarization and an increase in light transmittance. However, initiation and spread of AD across the layers of the somatosensory cortex, which is one of the most frequently affected brain regions in ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2017.00390
更新日期:2017-12-15 00:00:00
abstract::Loss of auditory sensory hair cells (HCs) is the most common cause of hearing loss. This review addresses the signaling pathways that are involved in the programmed and necrotic cell death of auditory HCs that occur in response to ototoxic and traumatic stressor events. The roles of inflammatory processes, oxidative s...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00096
更新日期:2015-03-31 00:00:00
abstract::Previous studies have demonstrated the presence of cannabinoid 2 receptor (CB2R) in the rat cochlea which was induced by cisplatin. In an organ of Corti-derived cell culture model, it was also shown that an agonist of the CB2R protected these cells against cisplatin-induced apoptosis. In the current study, we determin...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00271
更新日期:2018-08-21 00:00:00
abstract::The development of new techniques to study glial cells has revealed that they are active participants in the development of functional neuronal circuits. Calcium imaging studies demonstrate that glial cells actively sense and respond to neuronal activity. Glial cells can produce and release neurotransmitter-like molec...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2013.00039
更新日期:2013-04-23 00:00:00
abstract::Stressors, during early life or adulthood, can alter steroid-sensitive behaviors, such as exploration, anxiety, and/or cognitive processes. We investigated if exposure to acute stressors in adulthood may alter behavioral and neuroendocrine responses of male rats that were exposed to gestational stress or not. We hypot...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2012.00040
更新日期:2012-12-18 00:00:00
abstract::Germinal matrix hemorrhage (GMH) is a serious complication in extremely preterm infants associated with neurological deficits and mortality. The purpose of the present study was to develop and characterize a grade III and IV GMH model in postnatal day 5 (P5) rats, the equivalent of preterm human brain maturation. P5 W...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2020.535320
更新日期:2020-12-03 00:00:00
abstract::Manipulation of metabolic pathways (e.g., ketogenic diet (KD), glycolytic inhibition) alters neural excitability and represents a novel strategy for treatment of drug-refractory seizures. We have previously shown that inhibition of glycolysis suppresses epileptiform activity in hippocampal slices. In the present study...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00168
更新日期:2018-06-15 00:00:00
abstract::At the frog semicircular canals, the afferent fibers display high spontaneous activity (mEPSPs), due to transmitter release from hair cells. mEPSP and spike frequencies are modulated by stimulation that activates the hair cell receptor conductance. The relation between receptor current and transmitter release cannot b...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00235
更新日期:2015-06-23 00:00:00