Organic psychoses

Metabolic Disorders ◽

Antipsychotic Drugs ◽

Autoimmune Disorders ◽

Brain Diseases ◽

Organic Psychosis ◽

Organic Psychoses ◽

High Index Of Suspicion ◽

A psychosis is a syndrome characterized by delusions and hallucinations. Organic psychoses refer to those psychoses attributed to identifiable brain diseases andare thereby distinguished from primary psychoses such as schizophrenia. Almost any condition that affects the brain can cause an organic psychosis. Delirium and dementia are the most common, although there are many other causes including other neurodegenerative diseases, autoimmune disorders, multiple sclerosis, endocrinopathies, metabolic disorders, and infections. Making the diagnosis of an organic psychosis requires a high index of suspicion and appropriate investigation. The treatment is usually that of the primary disease when that is possible, while the symptoms of psychosis can be managed using antipsychotic drugs.

Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

Molecular Biomedicine ◽

10.1186/s43556-021-00040-5 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Jacopo Meldolesi

Keyword(s):

Multiple Sclerosis ◽

Extracellular Vesicles ◽

Brain Diseases ◽

Target Cells ◽

Surface Binding ◽

Cells Of Origin ◽

Relapsing Remitting ◽

And Function ◽

AbstractLast century, neurons and glial cells were mostly believed to play distinct functions, relevant for the brain. Progressively, however, it became clear that neurons, astrocytes and microglia co-operate intensely with each other by release/binding of signaling factors, direct surface binding and generation/release of extracellular vesicles, the exosomes and ectosomes, called together vesicles in this abstract. The present review is focused on these vesicles, fundamental in various brain diseases. Their properties are extraordinary. The specificity of their membrane governs their fusion with distinct target cells, variable depending on the state and specificity of their cells of origin and target. Result of vesicle fusion is the discharge of their cargos into the cytoplasm of target cells. Cargos are composed of critical molecules, from proteins (various nature and function) to nucleotides (especially miRNAs), playing critical roles in immune and neurodegenerative diseases. Among immune diseases is multiple sclerosis, affected by extensive dysregulation of co-trafficking neural and glial vesicles, with distinct miRNAs inducing severe or reducing effects. The vesicle-dependent differences between progressive and relapsing-remitting forms of the disease are relevant for clinical developments. In Alzheimer’s disease the vesicles can affect the brain by changing their generation and inducing co-release of effective proteins, such Aβ and tau, from neurons and astrocytes. Specific miRNAs can delay the long-term development of the disease. Upon their traffic through the blood-brainbarrier, vesicles of various origin reach fluids where they are essential for the identification of biomarkers, important for diagnostic and therapeutic innovations, critical for the future of many brain patients.

ATP-binding cassette transporters and neurodegenerative diseases

Essays in Biochemistry ◽

10.1042/ebc20210012 ◽

2021 ◽

Author(s):

Jared S. Katzeff ◽

Woojin Scott Kim

Keyword(s):

Abc Transporters ◽

Brain Diseases ◽

Atp Binding ◽

Future Directions ◽

Diverse Range ◽

The Brain ◽

Lateral Sclerosis ◽

Atp Binding Cassette

Abstract ATP-binding cassette (ABC) transporters are one of the largest groups of transporter families in humans. ABC transporters mediate the translocation of a diverse range of substrates across cellular membranes, including amino acids, nucleosides, lipids, sugars and xenobiotics. Neurodegenerative diseases are a group of brain diseases that detrimentally affect neurons and other brain cells and are usually associated with deposits of pathogenic proteins in the brain. Major neurodegenerative diseases include Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. ABC transporters are highly expressed in the brain and have been implicated in a number of pathological processes underlying neurodegenerative diseases. This review outlines the current understanding of the role of ABC transporters in neurodegenerative diseases, focusing on some of the most important pathways, and also suggests future directions for research in this field.

Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity

10.1101/2020.06.16.153981 ◽

2020 ◽

Author(s):

Laura Casares ◽

Juan Diego Unciti ◽

Maria Eugenia Prados ◽

Diego Caprioglio ◽

Maureen Higgins ◽

...

Keyword(s):

Oxidative Stress ◽

Multiple Sclerosis ◽

Cell Models ◽

Therapeutic Approaches ◽

Neuroprotective Effects ◽

Anti Oxidant ◽

Anti Inflammatory ◽

ABSTRACTOxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, Huntington’s and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington’s disease, setting the basis for further developments in vivo.

Microglia Specific Drug Targeting Using Natural Products for the Regulation of Redox Imbalance in Neurodegeneration

Frontiers in Pharmacology ◽

10.3389/fphar.2021.654489 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shashank Kumar Maurya ◽

Neetu Bhattacharya ◽

Suman Mishra ◽

Amit Bhattacharya ◽

Pratibha Banerjee ◽

...

Keyword(s):

Multiple Sclerosis ◽

Natural Products ◽

Molecular Mechanisms ◽

Immune Cell ◽

Neuroprotective Effect ◽

Inhibitory Effect ◽

Dual Function ◽

Redox Imbalance ◽

Microglia, a type of innate immune cell of the brain, regulates neurogenesis, immunological surveillance, redox imbalance, cognitive and behavioral changes under normal and pathological conditions like Alzheimer’s, Parkinson’s, Multiple sclerosis and traumatic brain injury. Microglia produces a wide variety of cytokines to maintain homeostasis. It also participates in synaptic pruning and regulation of neurons overproduction by phagocytosis of neural precursor cells. The phenotypes of microglia are regulated by the local microenvironment of neurons and astrocytes via interaction with both soluble and membrane-bound mediators. In case of neuron degeneration as observed in acute or chronic neurodegenerative diseases, microglia gets released from the inhibitory effect of neurons and astrocytes, showing activated phenotype either of its dual function. Microglia shows neuroprotective effect by secreting growths factors to heal neurons and clears cell debris through phagocytosis in case of a moderate stimulus. But the same microglia starts releasing pro-inflammatory cytokines like TNF-α, IFN-γ, reactive oxygen species (ROS), and nitric oxide (NO), increasing neuroinflammation and redox imbalance in the brain under chronic signals. Therefore, pharmacological targeting of microglia would be a promising strategy in the regulation of neuroinflammation, redox imbalance and oxidative stress in neurodegenerative diseases. Some studies present potentials of natural products like curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane to suppress activation of microglia. These natural products have also been proposed as effective therapeutics to regulate the progression of neurodegenerative diseases. The present review article intends to explain the molecular mechanisms and functions of microglia and molecular dynamics of microglia specific genes and proteins like Iba1 and Tmem119 in neurodegeneration. The possible interventions by curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane on microglia specific protein Iba1 suggest possibility of natural products mediated regulation of microglia phenotypes and its functions to control redox imbalance and neuroinflammation in management of Alzheimer’s, Parkinson’s and Multiple Sclerosis for microglia-mediated therapeutics.

Neural Stem Cells Therapy to Treat Neurodegenerative Diseases

E3S Web of Conferences ◽

10.1051/e3sconf/202127103076 ◽

2021 ◽

Vol 271 ◽

pp. 03076

Author(s):

Weibai Chen

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Neural Stem Cells ◽

Cell Transplantation ◽

Neural Stem Cell ◽

The Body ◽

Brain Diseases ◽

Neural stem cells have the ability to proliferation, differentiate and renew, which plays an important role in the growth, maturation and senescence of the human brain. But according to researches, neural stem cells in the brain do not remain active throughout an organism's lifetime. Many neural stem cells become dormant when the brain matures, and may be activated when the body is sick to selectively heal the disease. In recent years, there are many studies on neural stem cells. Joshua[1] and Ting Zhang[2] show that neurodegenerative diseases such as ischemic stroke, Alzheimer's disease and Parkinson's disease can be improved by the transplantation of neural stem cells, however the specific mechanism is not clear. This paper investigates three main questions: Why neural stem cell transplantation is chosen as a treatment? Where does NSCs derive from in clinical transplantation? How does neural stem cell transplantation treat brain diseases? And we also figure out the answers to these three questions. Firstly, transplantation of hypothalamic NSCs can delay the process of aging in the host, and Chemokines and EVs which secreted by neural stem cells can delay aging and defend neurodegenerative diseases. Secondly, the sources of NSCs can be divided into three types. The first is to isolate NSCs from primary tissue and cultivate them in vitro. The second is to produce the required cells by inducing pluripotent stem cells and embryonic stem cells. The third way to get NCS is through transdifferentiation of somatic cells. Thirdly, in brain diseases, transplanted NSCs can migrate from the aggregation site to the site of the disease, reducing damage to the blood-brain barrier, repairing learning and memory abilities that depend on the hippocampus and secreting neurotrophic factors.

Quantum Dots Application in Neurodegenerative Diseases

Thrita ◽

10.5812/thrita.100105 ◽

2021 ◽

Vol 9 (2) ◽

Author(s):

Behnam Hasannejadasl ◽

Farkhondeh Pooresmaeil Janbaz ◽

Edris Choupani ◽

Mahmood Fadaie ◽

Mohammad Ali Hamidinejad ◽

...

Keyword(s):

Multiple Sclerosis ◽

Quantum Dots ◽

Small Molecules ◽

Bright Light ◽

Therapeutic Agents ◽

High Quantum Yield ◽

High Emission ◽

Image Production ◽

: Quantum dots (QDs) are nanoparticles (NPs) with electronic and optical properties such as emitting bright light and fluorescence. They also carry specific characters such as photostability, high quantum yield, high emission, and size-turnable. Nowadays, a great interest is given to the extensive use of theranostic-NPs for sensing and imaging, as well as drug delivery. Moreover, QDs may yield great potential for the diagnosis and treatment of various central nervous system (CNS) diseases (e.g., Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis). The blood-brain barrier (BBB) protects the brain tissue. Only certain small molecules like water and gases can cross BBB, whereas larger molecules enter via receptors, but many drugs are incapable of passing the barrier. A series of great advances have been achieved concerning using different NPs (e.g., QDs) to deliver drugs to the brain and CNS imaging. In this review, we discussed a wide variety of QDs along with their production, passive or active delivery of therapeutic agents for neurodegenerative diseases, and different image production.

NAT8L mRNA oxidation is linked to neurodegeneration in multiple sclerosis

10.1101/2020.04.19.049494 ◽

2020 ◽

Author(s):

Prakash Kharel ◽

Naveen Kumar Singhal ◽

Nicole West ◽

Joram Rana ◽

Lindsey Smith ◽

...

Keyword(s):

Multiple Sclerosis ◽

Animal Model ◽

Aspartic Acid ◽

Neuronal Cells ◽

Underlying Mechanism ◽

Rna Oxidation ◽

The Brain ◽

Aspartate Transferase ◽

Cognate Protein

AbstractRNA oxidation has been implicated in neurodegeneration, but the underlying mechanism for such effects is unclear. Recently, we demonstrated extensive RNA oxidation within the neurons in multiple sclerosis (MS) brain. In this report we identified selectively oxidized mRNAs in neuronal cells that pertained to neuropathological pathways. N-acetyl aspartate transferase 8 like (NAT8L) mRNA is one such transcript, whose translated product enzymatically synthesizes N-acetyl aspartic acid (NAA), a neuronal metabolite important for myelin synthesis. We reasoned that impediment of translation of an oxidized NAT8L mRNA will result in reduction in its cognate protein, thus lowering NAA level. This assertion is directly supported by our studies on a model cellular system, an MS animal model and postmortem human MS brain. Reduced NAA level in the brain hampers myelin integrity making neuronal axons more susceptible to damage, which contributes in MS neurodegeneration. Overall, this work provides a framework for mechanistic understanding of the link between RNA oxidation and neurodegenerative diseases.

Role of Microglia Adenosine A2AReceptors in Retinal and Brain Neurodegenerative Diseases

Mediators of Inflammation ◽

10.1155/2014/465694 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 40

Author(s):

Ana R. Santiago ◽

Filipa I. Baptista ◽

Paulo F. Santos ◽

Gonçalo Cristóvão ◽

António F. Ambrósio ◽

...

Keyword(s):

Therapeutic Strategy ◽

Therapeutic Potential ◽

Brain Diseases ◽

Degenerative Diseases ◽

Chronic Neuroinflammation ◽

Retinal Degenerative Diseases ◽

G Protein Coupled ◽

Neuroinflammation mediated by microglial cells in the brain has been commonly associated with neurodegenerative diseases. Whether this microglia-mediated neuroinflammation is cause or consequence of neurodegeneration is still a matter of controversy. However, it is unequivocal that chronic neuroinflammation plays a role in disease progression and halting that process represents a potential therapeutic strategy. The neuromodulator adenosine emerges as a promising targeting candidate based on its ability to regulate microglial proliferation, chemotaxis, and reactivity through the activation of its G protein coupledA2Areceptor (A2AR). This is in striking agreement with the ability ofA2ARblockade to control several brain diseases. Retinal degenerative diseases have been also associated with microglia-mediated neuroinflammation, but the role ofA2ARhas been scarcely explored. This review aims to compare inflammatory features of Parkinson’s and Alzheimer’s diseases with glaucoma and diabetic retinopathy, discussing the therapeutic potential ofA2ARin these degenerative conditions.

Metal Imbalance in Neurodegenerative Diseases with a Specific Concern to the Brain of Multiple Sclerosis Patients

International Journal of Molecular Sciences ◽

10.3390/ijms21239105 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9105

Author(s):

Jean-Philippe Dales ◽

Sophie Desplat-Jégo

Keyword(s):

Multiple Sclerosis ◽

Drug Targets ◽

Chronic Inflammatory Disease ◽

Autoimmune Reaction ◽

Candidate Drug ◽

The Central Nervous System ◽

Multiple Sclerosis Patients ◽

There is increasing evidence that deregulation of metals contributes to a vast range of neurodegenerative diseases including multiple sclerosis (MS). MS is a chronic inflammatory disease of the central nervous system (CNS) manifesting disability and neurological symptoms. The precise origin of MS is unknown, but the disease is characterized by focal inflammatory lesions in the CNS associated with an autoimmune reaction against myelin. The treatment of this disease has mainly been based on the prescription of immunosuppressive and immune-modulating agents. However, the rate of progressive disability and early mortality is still worrisome. Metals may represent new diagnostic and predictive markers of severity and disability as well as innovative candidate drug targets for future therapies. In this review, we describe the recent advances in our understanding on the role of metals in brain disorders of neurodegenerative diseases and MS patients.

Microcirculation of the brain: morphological assessment in degenerative diseases and restoration processes

Reviews in the Neurosciences ◽

10.1515/revneuro-2014-0049 ◽

2015 ◽

Vol 26 (1) ◽

Cited By ~ 11

Author(s):

Yaroslav Kolinko ◽

Kristyna Krakorova ◽

Jan Cendelin ◽

Zbynek Tonar ◽

Milena Kralickova

Keyword(s):

Pathological Process ◽

Brain Diseases ◽

Degenerative Diseases ◽

Vascular Changes ◽

Brain Vessels ◽

Qualitative And Quantitative ◽

Quantitative Characteristics ◽

Brain Microcirculation ◽

AbstractBrain microcirculation plays an important role in the pathogenesis of various brain diseases. Several specific features of the circulation in the brain and its functions deserve special attention. The brain is extremely sensitive to hypoxia, and brain edema is more dangerous than edema in other tissues. Brain vessels are part of the blood-brain barrier, which prevents the penetration of some of the substances in the blood into the brain tissue. Herein, we review the processes of angiogenesis and the changes that occur in the brain microcirculation in the most prevalent neurodegenerative diseases. There are no uniform vascular changes in the neurodegenerative diseases. In some cases, the vascular changes are secondary consequences of the pathological process, but they could also be involved in the pathogenesis of the primary disease and contribute to the degeneration of neurons, based on their quantitative characteristics. Additionally, we described the stereological methods that are most commonly used for generating qualitative and quantitative data to assess changes in the microvascular bed of the brain.