Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction DOI Creative Commons
Paolo Calabresi, Alessandro Mechelli, Giuseppina Natale

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 1, 2023

Abstract Although the discovery of critical role α-synuclein (α-syn) in pathogenesis Parkinson’s disease (PD) is now twenty-five years old, it still represents a milestone PD research. Abnormal forms α-syn trigger selective and progressive neuronal death through mitochondrial impairment, lysosomal dysfunction, alteration calcium homeostasis not only but also other α-syn-related neurodegenerative disorders such as dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, REM sleep behavior disorder. Furthermore, α-syn-dependent early synaptic plastic alterations underlying mechanisms preceding overt neurodegeneration have attracted great interest. In particular, presence inflammation experimental models patients, occurring before deposition spreading α-syn, suggests mechanistic link between dysfunction. The knowledge these seminal importance to support research on reliable biomarkers precociously identify possible disease-modifying therapies targeting α-syn. this review, we will discuss issues, providing state art protein synucleinopathies.

Language: Английский

Magnesium in Man: Implications for Health and Disease DOI
Jeroen H. F. de Baaij, Joost G.J. Hoenderop, René J.M. Bindels

et al.

Physiological Reviews, Journal Year: 2014, Volume and Issue: 95(1), P. 1 - 46

Published: Dec. 24, 2014

Magnesium (Mg 2+ ) is an essential ion to the human body, playing instrumental role in supporting and sustaining health life. As second most abundant intracellular cation after potassium, it involved over 600 enzymatic reactions including energy metabolism protein synthesis. Although Mg availability has been proven be disturbed during several clinical situations, serum values are not generally determined patients. This review aims provide overview of function disease. In short, plays important physiological particularly brain, heart, skeletal muscles. Moreover, supplementation shown beneficial treatment of, among others, preeclampsia, migraine, depression, coronary artery disease, asthma. Over last decade, hereditary forms hypomagnesemia have deciphered, mutations transient receptor potential melastatin type 6 (TRPM6), claudin 16, cyclin M2 (CNNM2). Recently, transporter 1 (MagT1) were linked T-cell deficiency underlining cell viability. can consequence use certain types drugs, such as diuretics, epidermal growth factor inhibitors, calcineurin proton pump inhibitors. provides extensive comprehensive research few decades, focusing on regulation homeostasis intestine, kidney, bone disturbances which may result hypomagnesemia.

Language: Английский

Citations

1422
Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms DOI Open Access
Panos Zanos, Ruin Moaddel, Patrick J. Morris

et al.

Pharmacological Reviews, Journal Year: 2018, Volume and Issue: 70(3), P. 621 - 660

Published: June 26, 2018

Ketamine, a racemic mixture consisting of (S)- and (R)-ketamine, has been in clinical use since 1970. Although best characterized for its dissociative anesthetic properties, ketamine also exerts analgesic, anti-inflammatory, antidepressant actions. We provide comprehensive review these therapeutic uses, emphasizing drug dose, route administration, the time course effects. Dissociative, psychotomimetic, cognitive, peripheral side effects associated with short-term or prolonged exposure, as well recreational use, are discussed. further describe ketamine's pharmacokinetics, including rapid extensive metabolism to norketamine, dehydronorketamine, hydroxyketamine, hydroxynorketamine (HNK) metabolites. Whereas analgesic properties generally attributed direct ketamine-induced inhibition N-methyl-D-aspartate receptors, other putative lower-affinity pharmacological targets include, but not limited to, γ-amynobutyric acid (GABA), dopamine, serotonin, sigma, opioid, cholinergic voltage-gated sodium hyperpolarization-activated cyclic nucleotide-gated channels. examine evidence supporting relevance metabolites drug. Ketamine may have broader than was previously considered, given that HNK efficacy preclinical studies. Overall, target deconvolution will insight critical development new pharmacotherapies possess desirable ketamine, limit undesirable

Language: Английский

Citations

950
Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer DOI Open Access
Luca Colucci-D’Amato, Luisa Speranza, Floriana Volpicelli

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(20), P. 7777 - 7777

Published: Oct. 21, 2020

Brain-derived neurotrophic factor (BDNF) is one of the most distributed and extensively studied neurotrophins in mammalian brain. BDNF signals through tropomycin receptor kinase B (TrkB) low affinity p75 neurotrophin (p75NTR). plays an important role proper growth, development, plasticity glutamatergic GABAergic synapses modulation neuronal differentiation, it influences serotonergic dopaminergic neurotransmission. acts as paracrine autocrine factor, on both pre-synaptic post-synaptic target sites. It crucial transformation synaptic activity into long-term memories. considered instructive mediator functional structural central nervous system (CNS), influencing dendritic spines and, at least hippocampus, adult neurogenesis. Changes rate neurogenesis spine density can influence several forms learning memory contribute to depression-like behaviors. The possible roles highlighted this review focus effect antidepressant therapies BDNF-mediated plasticity. Moreover, we will data that illustrate a potent protective able confer protection against neurodegeneration, particular Alzheimer’s disease. Finally, give evidence how involvement pathogenesis brain glioblastoma has emerged, thus opening new avenues for treatment deadly cancer.

Language: Английский

Citations

648
The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain DOI Creative Commons
Jiyao Sheng,

Liu Shui,

Yicun Wang

et al.

Neural Plasticity, Journal Year: 2017, Volume and Issue: 2017, P. 1 - 10

Published: Jan. 1, 2017

Chronic pain, as a stress state, is one of the critical factors for determining depression, and their coexistence tends to further aggravate severity both disorders. Unfortunately, association remains unclear, which creates bottleneck problem managing chronic pain-induced depression. In recent years, studies have found considerable overlaps between pain- depression-induced neuroplasticity changes neurobiological mechanism changes. Such are vital facilitating occurrence development pain this review, we summarized role in two disorders question explored individualized application strategies analgesic drugs antidepressants that different pharmacological effects treatment Therefore, review may provide new insights into understanding

Language: Английский

Citations

642
Neuronal calcium signaling: function and dysfunction DOI
Marisa Brini, Tito Calì,

Denis Ottolini

et al.

Cellular and Molecular Life Sciences, Journal Year: 2014, Volume and Issue: 71(15), P. 2787 - 2814

Published: Jan. 18, 2014

Language: Английский

Citations

633
Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability DOI
Annamaria Vezzani, Barbara Viviani

Neuropharmacology, Journal Year: 2014, Volume and Issue: 96, P. 70 - 82

Published: Nov. 8, 2014

Language: Английский

Citations

555
Glutamatergic Signaling in the Central Nervous System: Ionotropic and Metabotropic Receptors in Concert DOI Creative Commons
Andreas Reiner, Joshua Levitz

Neuron, Journal Year: 2018, Volume and Issue: 98(6), P. 1080 - 1098

Published: June 1, 2018

Language: Английский

Citations

505
Extrasynaptic NMDA Receptor Involvement in Central Nervous System Disorders DOI Creative Commons
Matthew P. Parsons, Lynn A. Raymond

Neuron, Journal Year: 2014, Volume and Issue: 82(2), P. 279 - 293

Published: April 1, 2014

Language: Английский

Citations

495
NMDA receptor structures reveal subunit arrangement and pore architecture DOI

Chia-Hsueh Lee,

Wei Lü, Jennifer Carlisle Michel

et al.

Nature, Journal Year: 2014, Volume and Issue: 511(7508), P. 191 - 197

Published: June 20, 2014

Language: Английский

Citations

480
Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders DOI
Rui Gao, Peter Penzes

Current Molecular Medicine, Journal Year: 2015, Volume and Issue: 15(2), P. 146 - 167

Published: March 18, 2015

Autism Spectrum Disorders (ASD) and Schizophrenia (SCZ) are cognitive disorders with complex genetic architectures but overlapping behavioral phenotypes, which suggests common pathway perturbations. Multiple lines of evidence implicate imbalances in excitatory inhibitory activity (E/I imbalance) as a shared pathophysiological mechanism. Thus, understanding the molecular underpinnings E/I imbalance may provi de essential insight into etiology these uncover novel targets for future drug discovery. Here, we review key genetic, physiological, neuropathological, functional, studies that suggest alterations to excitatory/inhibitory circuits keys ASD SCZ pathogenesis. Keywords: Autism, dendritic spine, imbalance, GABAergic interneuron, glutamatergic, mTOR, NMDAR, schizophrenia.

Language: Английский

Citations

469