Comparison of the Long-Term Efficacy of Targeting the Subthalamic Nucleus Versus the Globus Pallidus Interna for Deep Brain Stimulation Treatment of Motor Dysfunction in Patients With Parkinson's Disease: A Meta-Analysis Study.

A cardinal symptom of Parkinson's disease (PD) is motor dysfunction, including bradykinesia and tremors, which is quantified in the Unified PD Rating Scale (UPDRS). Although some medications provide palliative treatments for these motor deficits, their efficacy wanes and can produce unwanted side effects, such as dyskinesia. Deep-brain stimulation (DBS) has provided an alternative treatment strategy that can benefit many patients, but optimal target structures for DBS and its long-term efficacy are not fully understood.

Glioblastoma therapy: State of the field and future prospects.

Glioblastoma (GB) is a cancerous brain tumor that originates from glial cells and leads to thousands of deaths each year and a five-year survival of only 6.8 %. Treatments for GB include surgery, chemotherapy, radiation, and immunotherapy.

Delivery of PAMAM dendrimers and dendriplexes across natural barriers (blood-brain barrier and placental barrier) in healthy pregnant mice.

Gene therapy is an important tool for treating fetal diseases that allows for the delivery and integration of therapeutic genes into the genome of cells carrying mutations. Nanomolecules, like PAMAM dendrimers, have recently come into wider use for carrying vectors as they have several advantages over viral vectors. Namely, (1) tunable size and surface chemistry, (2) uniform size, (3) the ability to target specific tissues, and (4) the ability to carry large biomolecules and drugs.

Presymptomatic Targeted Circuit Manipulation for Ameliorating Huntington's Disease Pathogenesis.

Early stages of Huntington's disease (HD) before the onset of motor and cognitive symptoms are characterized by imbalanced excitatory and inhibitory output from the cortex to striatal and subcortical structures. The window before the onset of symptoms presents an opportunity to adjust the firing rate within microcircuits with the goal of restoring the impaired E/I balance, thereby preventing or slowing down disease progression. Here, we investigated the effect of presymptomatic cell-type specific manipulation of activity of pyramidal neurons and parvalbumin interneurons in the M1 motor cortex on disease progression in the R6/2 HD mouse model.

Using microdialysis to monitor dopaminergic support of limb-use control following mesencephalic neurosphere transplantation in a rodent model of Parkinson's Disease.

Controlled nigrostriatal dopamine release supports effective limb use during locomotion coordination that becomes compromised after this pathway deteriorates in Parkinson's Disease (PD). How dopamine release relates to active ongoing behavior control remains unknown. Restoring proper release strategy appears important to successful PD treatment with transplanted dopamine-producing stem cells.

Correction: Bowers et al. Tart Cherry Extract and Omega Fatty Acids Reduce Behavioral Deficits and Gliosis in the 5xFAD Mouse Model of Alzheimer's Disease. 2021, , 1423.

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Inducible Knockout of 14-3-3β Attenuates Proliferation and Spheroid Formation in a Human Glioblastoma Cell Line U87MG.

Glioblastomas (GBs) are the most common and malignant brain tumors in adults. A protein encoded by the gene YWHAB, 14-3-3β, is commonly found to be upregulated throughout the initiation and progression of GB. The 14-3-3β has oncogenic roles in several different types of cancer cells through interactions with proteins such as Bad, FBI1, Raf-1, Cdc25b, and others.

Tart Cherry Extract and Omega Fatty Acids Reduce Behavioral Deficits, Gliosis, and Amyloid-Beta Deposition in the 5xFAD Mouse Model of Alzheimer's Disease.

Combined treatments using polyphenols and omega fatty acids provide several therapeutic benefits for a variety of age-related disorders, including Alzheimer's disease (AD). Previously, we found a commercial product, Total Body Rhythm (TBR), consisting of tart cherry extract, a potent polyphenol, and omega fatty acids, significantly reduced memory, and neuropathological deficits in the 192 IgG-saporin mouse model of AD. The present study assessed the efficacy of TBR for treating behavioral and neuropathological deficits in the 5xFAD model of AD.

Tetrahydrocurcumin Has Similar Anti-Amyloid Properties as Curcumin: In Vitro Comparative Structure-Activity Studies.

Despite its potent anti-amyloid properties, the utility of curcumin (Cur) for the treatment of Alzheimer's disease (AD) is limited due to its low bioavailability. Tetrahydrocurcumin (THC), a more stable metabolite has been found in Cur-treated tissues. We compared the anti-amyloid and neuroprotective properties of curcumin, bisdemethoxycurcumin (BDMC), demethoxycurcumin (DMC) and THC using molecular docking/dynamics, in-silico and in vitro studies.

Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines.

Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state.

Housing R6/2 Mice with Wild-Type Littermates Increases Lifespan.

The R6/2 murine model of Huntington's disease (HD) is extensively used in HD research. The current study replicates and extends previous work assessing the impact of housing R6/2 mice with healthy wild-type (WT) littermates on disease progression. The current study extends the previous finding by including male cohorts and the use of a standard diet and water regimen, as opposed to the enhanced diet used in the previous study.

Curcugreen Treatment Prevented Splenomegaly and Other Peripheral Organ Abnormalities in 3xTg and 5xFAD Mouse Models of Alzheimer's Disease.

Metabolic dysfunction and immune disorders are common in Alzheimer's disease (AD). The mechanistic details of these epiphenomena in AD are unclear. Here, we have investigated whether a highly bioavailable curcuminoid formulation, curcugreen (CGR), can prevent abnormalities in peripheral organs of two mouse models of AD.

Modeling Neurological Disorders in 3D Organoids Using Human-Derived Pluripotent Stem Cells.

Modeling neurological disorders is challenging because they often have both endogenous and exogenous causes. Brain organoids consist of three-dimensional (3D) self-organizing brain tissue which increasingly is being used to model various aspects of brain development and disorders, such as the generation of neurons, neuronal migration, and functional networks. These organoids have been recognized as important tools to model developmental features of the brain, including neurological disorders, which can provide insights into the molecular mechanisms involved in those disorders.

Carnosine improves aging-induced cognitive impairment and brain regional neurodegeneration in relation to the neuropathological alterations in the secondary structure of amyloid beta (Aβ).

Aging-induced proteinopathies, including deterioration of amyloid beta (Aβ) conformation, are associated with reductions in endogenous levels of carnosine and cognitive impairments. Carnosine is a well-known endogenous antioxidant, which counteracts aging-induced Aβ plaque formation. The aim of this study was to investigate the effects of exogenous carnosine treatments on aging-induced changes (a) in the steady-state level of endogenous carnosine and conformation of Aβ secondary structure in the different brain regions (cerebral cortex, hippocampus, hypothalamus, pons-medulla, and cerebellum) and (b) cognitive function.

Preservation of dendritic spine morphology and postsynaptic signaling markers after treatment with solid lipid curcumin particles in the 5xFAD mouse model of Alzheimer's amyloidosis.

Background: Synaptic failure is one of the principal events associated with cognitive dysfunction in Alzheimer's disease (AD). Preservation of existing synapses and prevention of synaptic loss are promising strategies to preserve cognitive function in AD patients. As a potent natural anti-oxidant, anti-amyloid, and anti-inflammatory polyphenol, curcumin (Cur) shows great promise as a therapy for AD.

Liraglutide Has Anti-Inflammatory and Anti-Amyloid Properties in Streptozotocin-Induced and 5xFAD Mouse Models of Alzheimer's Disease.

Recent clinical and epidemiological studies support the contention that diabetes mellitus (DM) is a strong risk factor for the development of Alzheimer's disease (AD). The use of insulin cell toxin, streptozotocin (STZ), when injected into the lateral ventricles, develops an insulin resistant brain state (IRBS) and represents a non-transgenic, or sporadic AD model (SAD), with several AD-like neuropathological features. The present study explored the effects of an anti-diabetic drug, liraglutide (LIR), in reversing major pathological hallmarks in the prodromal disease stage of both the 5xFAD transgenic and SAD mouse models of AD.

Solid Lipid Curcumin Particles Protect Medium Spiny Neuronal Morphology, and Reduce Learning and Memory Deficits in the YAC128 Mouse Model of Huntington's Disease.

Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by massive neuronal degeneration in the striatum. In this study, we utilized solid lipid curcumin particles (SLCPs) and solid lipid particles (SLPs) to test their efficacy in reducing deficits in YAC128 HD mice. Eleven-month-old YAC128 male and female mice were treated orally with SLCPs (100 mg/kg) or equivalent volumes of SLPs or vehicle (phosphate-buffered saline) every other day for eight weeks.

Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by amyloid (Aβ) aggregation, hyperphosphorylated tau, neuroinflammation, and severe memory deficits. Reports that certain boronic compounds can reduce amyloid accumulation and neuroinflammation prompted us to compare trans-2-phenyl-vinyl-boronic-acid-MIDA-ester (TPVA) and trans-beta-styryl-boronic-acid (TBSA) as treatments of deficits in in vitro and in vivo models of AD. We hypothesized that these compounds would reduce neuropathological deficits in cell-culture and animal models of AD.

A Mixed-Surface Polyamidoamine Dendrimer for In Vitro and In Vivo Delivery of Large Plasmids.

Drug delivery to the brain is highly hindered by the presence of the blood-brain barrier (BBB), which prevents the entry of many potential drugs/biomolecules into the brain. One of the current strategies to achieve gene therapy for neurodegenerative diseases involves direct injection of a viral vector into the brain. There are various disadvantages of viral vectors, including limitations of cargo size and safety concerns.

Possible roles of epigenetics in stem cell therapy for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease with loss of dopaminergic neurons. PD has genetic and epigenetic influences that determine specific changes in the brain. Epigenetic changes result in defective methylation of genes leading to differential gene-expression causing PD.

PAMAM Dendrimer Nanomolecules Utilized as Drug Delivery Systems for Potential Treatment of Glioblastoma: A Systematic Review.

Glioblastoma (GB) is a grade IV astrocytoma that maintains a poor prognosis with respect to current treatment options. Despite major advancements in the fields of surgery and chemoradiotherapy over the last few decades, the life expectancy for someone with glioblastoma remains virtually unchanged and warrants a new approach for treatment. Poly(amidoamine) (PAMAM) dendrimers are a type of nanomolecule that ranges in size (between 1 and 100 nm) and shape and can offer a new viable solution for the treatment of intracranial tumors, including glioblastoma.