Neurotherapeutics

http://link.springer.com/journal/13311

List of Papers (Total 761)

Pridopidine Induces Functional Neurorestoration Via the Sigma-1 Receptor in a Mouse Model of Parkinson’s Disease

Pridopidine is a small molecule in clinical development for the treatment of Huntington’s disease. It was recently found to have high binding affinity to the sigma-1 receptor, a chaperone protein involved in cellular defense mechanisms and neuroplasticity. Here, we have evaluated the neuroprotective and neurorestorative effects of pridopidine in a unilateral 6-hydroxydopamine (6...

Oligonucleotide Therapeutics as a New Class of Drugs for Malignant Brain Tumors: Targeting mRNAs, Regulatory RNAs, Mutations, Combinations, and Beyond

Malignant brain tumors are rapidly progressive and often fatal owing to resistance to therapies and based on their complex biology, heterogeneity, and isolation from systemic circulation. Glioblastoma is the most common and most aggressive primary brain tumor, has high mortality, and affects both children and adults. Despite significant advances in understanding the pathology...

Herpes Infections and Dementia: Rebutting Alternative Fact

Recent commentary in Neurotherapeutics by Nath critically addresses the earlier report by Tzeng et al. that aggressive antiviral treatment (AVT) against herpes simplex virus (HSV) was associated with a later decrease in the incidence of Alzheimer’s disease (AD). Nath raises issues that we respond to: we point out that (i) the treated group (probably with severe infection) is...

Genetics, Mechanisms, and Therapeutic Progress in Polyglutamine Spinocerebellar Ataxias

Autosomal dominant cerebellar ataxias (ADCAs) are a group of neurodegenerative disorders characterized by degeneration of the cerebellum and its connections. All ADCAs have progressive ataxia as their main clinical feature, frequently accompanied by dysarthria and oculomotor deficits. The most common spinocerebellar ataxias (SCAs) are 6 polyglutamine (polyQ) SCAs. These diseases...

Optimizing Trajectories for Cranial Laser Interstitial Thermal Therapy Using Computer-Assisted Planning: A Machine Learning Approach

Laser interstitial thermal therapy (LITT) is an alternative to open surgery for drug-resistant focal mesial temporal lobe epilepsy (MTLE). Studies suggest maximal ablation of the mesial hippocampal head and amygdalohippocampal complex (AHC) improves seizure freedom rates while better neuropsychological outcomes are associated with sparing of the parahippocampal gyrus (PHG...

L-Norvaline Reverses Cognitive Decline and Synaptic Loss in a Murine Model of Alzheimer’s Disease

The urea cycle is strongly implicated in the pathogenesis of Alzheimer’s disease (AD). Arginase-I (ARGI) accumulation at sites of amyloid-beta (Aβ) deposition is associated with L-arginine deprivation and neurodegeneration. An interaction between the arginase II (ARGII) and mTOR-ribosomal protein S6 kinase β-1 (S6K1) pathways promotes inflammation and oxidative stress. In this...

Inhibition of MyD88 Signaling Skews Microglia/Macrophage Polarization and Attenuates Neuronal Apoptosis in the Hippocampus After Status Epilepticus in Mice

Inflammation is implicated in epileptogenesis. Activated microglia and macrophages (MG/MΦ) are found in the brains of patients with epilepsy-related diseases and animal models of epilepsy. It is not yet known how the MG/MΦ activation phenotype affects pathological changes in the brain after a single seizure. In this study, we had 2 main purposes: first, to characterize post...

Angiotensin Type 1 Receptor Antagonists Protect Against Alpha-Synuclein-Induced Neuroinflammation and Dopaminergic Neuron Death

The loss of dopaminergic neurons and α-synuclein accumulation are major hallmarks of Parkinson’s disease (PD), and it has been suggested that a major mechanism of α-synuclein toxicity is microglial activation. The lack of animal models that properly reproduce PD, and particularly the underlying synucleinopathy, has hampered the clarification of PD mechanisms and the development...

Now is the Critical Time for Engineered Neuroplasticity

Recent advances in neuroscience and devices are ushering in a new generation of medical treatments. Engineered biodevices are demonstrating the potential to create long-term changes in neural circuits, termed neuroplasticity. Thus, the approach of engineering neuroplasticity is rapidly expanding, building on recent demonstrations of improved quality of life for people with...

Advances and Limitations of Current Epigenetic Studies Investigating Mammalian Axonal Regeneration

SummaryAxonal regeneration relies on the expression of regenerative associated genes within a coordinated transcriptional programme, which is finely tuned as a result of the activation of several regenerative signalling pathways. In mammals, this chain of events occurs in neurons following peripheral axonal injury, however it fails upon axonal injury in the central nervous system...

Chronic Administration of Pimozide Fails to Attenuate Motor and Pathological Deficits in Two Mouse Models of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which presently does not have any efficient therapeutic approach. Pimozide, a Food and Drug Administration (FDA)-approved neuroepileptic drug, has been recently proposed as a promising treatment for ALS patients based on apparent stabilization of right hand muscles after a short-time administration. A new...

Pigment Epithelium-Derived Factor Plays a Role in Alzheimer’s Disease by Negatively Regulating Aβ42

Alzheimer’s disease (AD) is the most common cause of dementia. Pigment epithelium-derived factor (PEDF), a unique neurotrophic protein, decreases with aging. Previous reports have conflicted regarding whether the PEDF concentration is altered in AD patients. In addition, the effect of PEDF on AD has not been documented. Here, we tested serum samples of 31 AD patients and 271...

Non-Pharmacological Approaches for Migraine

Migraine is one of the most common and debilitating neurological disorders. However, the efficacy of pharmacological therapies may have unsatisfactory efficacy and can be poorly tolerated. There is a strong need in clinical practice for alternative approaches for both acute and preventive treatment. Occasionally, this need might arise in the context of low-frequency migraneurs...

Targeted CGRP Small Molecule Antagonists for Acute Migraine Therapy

Migraine is a highly prevalent, severe, and disabling neurological condition with a significant unmet need for effective acute therapies. Patients (~50%) are dissatisfied with their currently available therapies. Calcitonin gene-related peptide (CGRP) has emerged as a key neuropeptide involved in the pathophysiology of migraines. As reviewed in this manuscript, a number of small...

Targeted Acid-Sensing Ion Channel Therapies for Migraine

Acid-sensing ion channels (ASICs) are a family of ion channels, consisting of four members; ASIC1 to 4. These channels are sensitive to changes in pH and are expressed throughout the central and peripheral nervous systems—including brain, spinal cord, and sensory ganglia. They have been implicated in a number of neurological conditions such as stroke and cerebral ischemia...

Therapeutic Approaches for the Management of Trigeminal Autonomic Cephalalgias

Trigeminal autonomic cephalalgia (TAC) encompasses 4 unique primary headache types: cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms. They are grouped on the basis of their shared...

Intrinsic Inflammation Is a Potential Anti-Epileptogenic Target in the Organotypic Hippocampal Slice Model

Understanding the mechanisms of epileptogenesis is essential to develop novel drugs that could prevent or modify the disease. Neuroinflammation has been proposed as a promising target for therapeutic interventions to inhibit the epileptogenic process that evolves from traumatic brain injury. However, it remains unclear whether cytokine-related pathways, particularly TNF...

Targeted Orexin and Hypothalamic Neuropeptides for Migraine

The hypothalamus is involved in the regulation of homeostatic mechanisms and migraine-related trigeminal nociception and as such has been hypothesized to play a central role in the migraine syndrome from the earliest stages of the attack. The hypothalamus hosts many key neuropeptide systems that have been postulated to play a role in this pathophysiology. Such neuropeptides...

Gut Microbiota and the Neuroendocrine System

The microbial ecosystem that inhabits the gastrointestinal tract of all mammals—the gut microbiota—has been in a symbiotic relationship with its hosts over many millennia. Thanks to modern technology, the myriad of functions that are controlled or modulated by the gut microbiota are beginning to unfold. One of the systems that is emerging to closely interact with the gut...