Abstract:
:There is currently no therapeutic drug treatment for traumatic brain injury (TBI) despite decades of experimental clinical trials. This may be because the mechanistic pathways for improving TBI outcomes have yet to be identified and exploited. As such, there remains a need to seek out new molecular targets and their drug candidates to find new treatments for TBI. This review presents supporting evidence for cathepsin B, a cysteine protease, as a potentially important drug target for TBI. Cathepsin B expression is greatly up-regulated in TBI animal models, as well as in trauma patients. Importantly, knockout of the cathepsin B gene in TBI mice results in substantial improvements of TBI-caused deficits in behavior, pathology, and biomarkers, as well as improvements in related injury models. During the process of TBI-induced injury, cathepsin B likely escapes the lysosome, its normal subcellular location, into the cytoplasm or extracellular matrix (ECM) where the unleashed proteolytic power causes destruction via necrotic, apoptotic, autophagic, and activated glia-induced cell death, together with ECM breakdown and inflammation. Significantly, chemical inhibitors of cathepsin B are effective for improving deficits in TBI and related injuries including ischemia, cerebral bleeding, cerebral aneurysm, edema, pain, infection, rheumatoid arthritis, epilepsy, Huntington's disease, multiple sclerosis, and Alzheimer's disease. The inhibitor E64d is unique among cathepsin B inhibitors in being the only compound to have demonstrated oral efficacy in a TBI model and prior safe use in man and as such it is an excellent tool compound for preclinical testing and clinical compound development. These data support the conclusion that drug development of cathepsin B inhibitors for TBI treatment should be accelerated.
journal_name
Front Neuroljournal_title
Frontiers in neurologyauthors
Hook G,Jacobsen JS,Grabstein K,Kindy M,Hook Vdoi
10.3389/fneur.2015.00178subject
Has Abstractpub_date
2015-09-02 00:00:00pages
178issn
1664-2295journal_volume
6pub_type
杂志文章,评审abstract::The interaction of Mesial Temporal Lobe Epilepsy (mTLE) with the circadian system control is apparent from an oscillatory pattern of limbic seizures, daytime's effect on seizure onset and the efficacy of antiepileptic drugs. Moreover, seizures per se can interfere with the biological rhythm output, including circadian...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.00632
更新日期:2018-08-02 00:00:00
abstract::Background: Transcranial direct current stimulation (tDCS) and therapy-based virtual reality (VR) have been investigated separately. They have shown promise as efficient and engaging new tools in the neurological rehabilitation of individuals with cerebral palsy (CP). However, the recent literature encourages investig...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.00953
更新日期:2020-09-02 00:00:00
abstract::Background: Caregiver strain is recognized globally with Parkinson's disease (PD). Comparatively little is understood about caregiver burden and strain in Asia. Objective: To investigate caregiver strain for families living with PD in Singapore, in light of international data. Methods: Ninety-four caregivers were recr...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.00455
更新日期:2020-06-23 00:00:00
abstract::Mitochondrial complex III deficiency nuclear type 2 is an autosomal-recessive disorder caused by mutations in TTC19 gene. TTC19 is involved in the preservation of mitochondrial complex III, which is responsible for transfer of electrons from reduced coenzyme Q to cytochrome C and thus, contributes to the formation of ...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2019.00944
更新日期:2019-09-04 00:00:00
abstract::Sudden infant death syndrome (SIDS) is the unexplained death, usually during sleep, of a baby younger than 1-year-old. Even though researchers have discovered some factors that may put babies at extra risk, SIDS remains unpredictable up until now. One hypothesis is that impaired cardiovascular control may play a role ...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2016.00236
更新日期:2016-12-23 00:00:00
abstract:OBJECTIVE:Our aim was to identify the role of the investigators' knowledge of the patient's history of vestibular symptoms (PVH) in the clinical evaluation of the bedside head-impulse test (bHIT). We hypothesized that this knowledge will reduce uncertainty and improve bHIT accuracy when compared to quantitative analysi...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2017.00051
更新日期:2017-02-20 00:00:00
abstract::Background: This study's aim was to investigate a large cohort of dystonia patients for pathogenic and rare variants in the ATM gene, making use of a new, cost-efficient enrichment technology for NGS-based screening. Methods: Single molecule Molecular Inversion Probes (smMIPs) were used for targeted enrichment and seq...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.01332
更新日期:2019-12-18 00:00:00
abstract::Thyroid hormones are of fundamental importance for brain development and essential factors to warrant brain functions throughout life. Their actions are mediated by binding to specific intracellular and membranous receptors regulating genomic and non-genomic mechanisms in neurons and populations of glial cells, respec...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2019.01103
更新日期:2019-10-18 00:00:00
abstract::Background: The sequence effect (SE), referring to step-to-step reduction in amplitude, is considered to lead to freezing of gait (FOG) in Parkinson's disease (PD). Visual cues may alleviate SE and help reduce freezing episodes. FOG patients show significant SE prior to turning or toward a doorway, but the SE toward a...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.00838
更新日期:2020-08-12 00:00:00
abstract::The vestibulo-ocular reflex (VOR) consists of two components, the rotational VOR (rVOR) elicited by semicircular canal signals and the translational VOR (tVOR) elicited by otolith signals. Given the relevant role of the vertical tVOR in human walking, this study aimed at measuring the time delay of eye movements in re...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.00332
更新日期:2020-05-14 00:00:00
abstract::Background: Following aneurysmal subarachnoid hemorrhage, peripherally-drawn lactic acid has been associated with poor outcomes; however, its clinical significance is unknown. We investigated admission factors and patient outcomes associated with serum lactic acid in this population. Methods: This was a retrospective ...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.00593
更新日期:2018-07-23 00:00:00
abstract::Background: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. The clinical manifestations of NIID are complex and easily misdiagnosed. Based on the current knowledge of this disease, it is usually chronic, with almost no acute cases. Stroke-like disease is an extremely rare type of NI...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2020.00530
更新日期:2020-06-10 00:00:00
abstract::Background: Essential tremor (ET) is a common, progressive neurological syndrome with bilateral upper-limb dysfunction of at least 3-year duration, with or without tremor in other body locations. This disorder has a negative impact on daily function and quality of life. A single oral therapy has been approved by FDA f...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00597
更新日期:2019-06-11 00:00:00
abstract::Background: Increasing evidence indicates that early radiation-induced subtle cerebral changes may be the precursors to permanent brain dysfunction at the late-delayed (LDS) post-radiotherapy (RT) stage. In this study, we aim to track the RT-related longitudinal brain activity in nasopharyngeal carcinoma (NPC) patient...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00752
更新日期:2019-07-16 00:00:00
abstract::Ictal fear-a relatively rare phenomenon-is a semiological characteristic of epilepsy. Most patients with epilepsy with ictal fear have an epileptic zone in the mesial temporal lobe, which is the classical brain area involved in emotion processing. Herein, we report a case of epilepsy with ictal fear as the first manif...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2018.00644
更新日期:2018-08-07 00:00:00
abstract::Background and aims: The pathophysiology of hippocampal enlarged perivascular spaces (H-EPVS) and its relationship to cognitive impairment is largely unknown. This study aimed to investigate the relationship between H-EPVS and cognition in non-dementic elderly population. Methods: A total of 109 subjects were prospect...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.542511
更新日期:2020-09-29 00:00:00
abstract::Motion perception following rotational vestibular stimulation is described either as a self-motion or as an environmental-motion. The purpose of the present study was to establish frequency of occurrence of both sensations in healthy humans; what other sensations they experience and how factors insinuation and visual ...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00162
更新日期:2019-02-27 00:00:00
abstract::Hyperbaric oxygen (HBO) therapy has been suggested a treatment option in order to reduce the development of secondary insults succeeding traumatic brain injury. This case report studied the course of a 23-year-old gentleman with a close range transhemispheric gunshot wound. The biochemical parameters, using a multi-mo...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2015.00062
更新日期:2015-03-23 00:00:00
abstract::Moderate-severe traumatic brain injury (TBI) may result in difficulty with emotion recognition, which has negative implications for social functioning. As aspects of social cognition have been linked to resting-state functional connectivity (RSFC) in the default mode network (DMN), we sought to determine whether DMN c...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00825
更新日期:2019-08-09 00:00:00
abstract::Background: Better upper limb recovery after stroke could be achieved through tailoring rehabilitation interventions directly at movement deficits. Aim: To identify potential; targets for therapy by synthesizing findings of differences in kinematics and muscle activity between stroke survivors and healthy adults perfo...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.00472
更新日期:2018-06-25 00:00:00
abstract::Background: This study aims to investigate the association between blood pressure (BP) at the time of recanalization and hemorrhagic transformation in large vessel occlusion (LVO) patients following mechanical thrombectomy (MT) with general anesthesia. Methods: We retrospectively reviewed our data base for patients wi...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.582639
更新日期:2020-11-17 00:00:00
abstract::Traumatic brain injury (TBI) is a major cause of death worldwide. Depending on the severity of the injury, TBI can reflect a broad range of consequences such as speech impairment, memory disturbances, and premature death. In this study, embryonic neural stem cells (ENSC) were isolated from E14 mouse embryos and cultur...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2018.00895
更新日期:2018-10-24 00:00:00
abstract::Objective: Status epilepticus is a major emergency condition. The choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial, including levetiracetam vs. fosphenytoin. We compare the safety of intravenous levetiracetam and fosphenytoin as a second-line treatment in patients with...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.00615
更新日期:2020-07-02 00:00:00
abstract:Introduction:The current standard treatment for patients with Duchenne muscular dystrophy (DMD) involves corticosteroids. Granulocyte colony-stimulating factor (G-CSF) induces the proliferation of satellite cells and myoblasts and, in turn, muscle regeneration. Beneficial effects of G-CSF were also described for skelet...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2017.00566
更新日期:2017-10-26 00:00:00
abstract::Sleep complaints increase profoundly with age; prevalence estimates of insomnia in the elderly reach up to 37%. The three major types of nocturnal complaints are difficulties initiating (DIS) and maintaining (DMS) sleep and early morning awakening (EMA), of which the latter appears most characteristic for aging. The n...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2012.00105
更新日期:2012-06-28 00:00:00
abstract::Migraine is a chronic disease characterized by unilateral, pulsating, and often moderate-to-severe recurrent episodes of headache with nausea and vomiting. It affects approximately 15% of the general population, yet the underlying pathophysiological mechanisms are not fully understood. Optical coherence tomography (OC...
journal_title:Frontiers in neurology
pub_type: 杂志文章,评审
doi:10.3389/fneur.2017.00684
更新日期:2017-12-13 00:00:00
abstract::Autism Spectrum Disorders comprise conditions that may affect cognitive development, motor skills, social interaction, communication, and behavior. This set of functional deficits often results in lack of independence for the diagnosed individuals, and severe distress for patients, families, and caregivers. There is a...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.01145
更新日期:2019-10-31 00:00:00
abstract::Recovery after surgical reconstruction of a brachial plexus injury using nerve grafting and nerve transfer procedures is a function of peripheral nerve regeneration and cerebral reorganization. A 15-year-old boy, with traumatic avulsion of nerve roots C5-C7 and a non-rupture of C8-T1, was operated 3 weeks after the in...
journal_title:Frontiers in neurology
pub_type:
doi:10.3389/fneur.2017.00072
更新日期:2017-03-03 00:00:00
abstract::Background: Agoraphobia was described in 1871 as a condition of fear-related alterations in spatial orientation and locomotor control triggered by places or situations that might cause a patient to panic and feel trapped. In contemporary nosology, however, this original concept of agoraphobia was split into two diagno...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2019.00874
更新日期:2019-08-13 00:00:00
abstract::Background and Purpose: The relationship between cerebral microbleeds (CMBs) and prognosis in patients with ischemic stroke is still unclear. Our aim here was to verify the relationship between CMBs and functional outcomes in patients with minor ischemic stroke treated with antiplatelet therapy. Methods: We retrospect...
journal_title:Frontiers in neurology
pub_type: 杂志文章
doi:10.3389/fneur.2020.00522
更新日期:2020-06-16 00:00:00