Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling

Mitochondrion, Journal Year: 2019, Volume and Issue: 49, P. 35 - 45

Published: July 6, 2019

Language: Английский

---

Metal Drugs and the Anticancer Immune Response

Chemical Reviews, Journal Year: 2018, Volume and Issue: 119(2), P. 1519 - 1624

Published: Nov. 29, 2018

The immune system deploys a multitude of innate and adaptive mechanisms not only to ward off pathogens but also prevent malignant transformation ("immune surveillance"). Hence, clinically apparent tumor already reflects selection for those cell clones capable evading recognition evasion"). Metal drugs, besides their well-investigated cytotoxic anticancer effects, massively interact with the cancer-immune interface can reverse important aspects evasion. This topic has recently gained intense attention based on combination approaches immunotherapy (e.g., checkpoint inhibitors), strategy delivering first exciting results in clinical settings. review summarizes promising still extremely fragmentary knowledge interplay metal drugs fidelity responses role adverse effects. It highlights that, at least some cases, induce long-lasting responses. Important steps this process comprise altered visibility susceptibility cancer cells toward immunity, as well direct impacts populations microenvironment. On basis gathered information, we suggest initiating joint multidisciplinary programs implement comprehensive analyses into strategies develop novel smart compounds.

Language: Английский

---

Pharmacology of Medical Cannabis

Advances in experimental medicine and biology, Journal Year: 2019, Volume and Issue: unknown, P. 151 - 165

Published: Jan. 1, 2019

Language: Английский

---

The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond

CNS Drugs, Journal Year: 2021, Volume and Issue: 35(9), P. 935 - 963

Published: June 18, 2021

Epilepsy is one of the most common and disabling chronic neurological disorders. Antiseizure medications (ASMs), previously referred to as anticonvulsant or antiepileptic drugs, are mainstay symptomatic epilepsy treatment. a multifaceted complex disease so its Currently, about 30 ASMs available for therapy. Furthermore, several approved therapies in nonepileptic conditions, including neuropathic pain, migraine, bipolar disorder, generalized anxiety disorder. Because this wide spectrum therapeutic activity, among often prescribed centrally active agents. Most act by modulation voltage-gated ion channels; enhancement gamma aminobutyric acid-mediated inhibition; through interactions with elements synaptic release machinery; blockade ionotropic glutamate receptors; combinations these mechanisms. differences their mechanisms action, do not suppress all types seizures, appropriate treatment choices important. The goal therapy complete elimination seizures; however, achievable one-third patients. Both vivo vitro models seizures used discover that more effective patients continued drug-resistant seizures. specific etiology being developed. ~ new compounds diverse antiseizure preclinical clinical drug development pipeline. Moreover, potential antiepileptogenic disease-modifying effects development. Overall, world changing evolving many exciting important ways. However, while developed, knowledge pharmacokinetics, efficacy spectrum, adverse effect profiles currently an essential component treating successfully maintaining high quality life every patient, particularly those receiving polypharmacy

Language: Английский

---

Substance P and pain chronicity

Cell and Tissue Research, Journal Year: 2018, Volume and Issue: 375(1), P. 227 - 241

Published: Oct. 3, 2018

Substance P (SP) is a highly conserved member of the tachykinin peptide family that widely expressed throughout animal kingdom. The numerous members are involved in multitude neuronal signaling pathways, mediating sensations and emotional responses (Steinhoff et al. Physiol Rev 94:265–301, 2014). In contrast to receptors for classical transmitters, such as glutamate (Parsons Handb Exp Pharmacol 249–303, 2005), only minority neurons certain brain areas express neurokinin (NKRs) (Mantyh J Clin Psychiatry 63:6–10, 2002). SP also by variety non-neuronal cell types microglia, well immune cells (Mashaghi Cell Mol Life Sci 73:4249–4264, 2016). an 11-amino acid neuropeptide preferentially activates neurokinin-1 receptor (NK1R). It transmits nociceptive signals via primary afferent fibers spinal brainstem second-order (Cao Nature 392:390–394, 1998). Compounds inhibit SP's action being investigated potential drugs relieve pain. More recently, NKR have gained attention their role complex psychiatric processes. key goal field pain research understand mechanisms transition between acute chronic influence cognitive inputs feedbacks from different makes not perception but experience (Zieglgänsberger CNS Spectr 10:298–308, 2005; Trenkwaldner Sleep Med 31:78–85, 2017). This review focuses on functional plasticity dorsal horn major relay information.

Language: Английский

---

Chronic Orofacial Pain: Models, Mechanisms, and Genetic and Related Environmental Influences

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(13), P. 7112 - 7112

Published: July 1, 2021

Chronic orofacial pain conditions can be particularly difficult to diagnose and treat because of their complexity limited understanding the mechanisms underlying aetiology pathogenesis. Furthermore, there is considerable variability between individuals in susceptibility risk factors predisposing them development maintenance chronic as well expression features such allodynia, hyperalgesia extraterritorial sensory spread. The suggests that genetic environmental may contribute pain. This article reviews these pain, outlines findings from studies animal models behavioural characteristics related trigeminal neuropathic particular. review also considers role especially models, focussing on differences strains These are not only relevant patients development, but underscore importance for considering strain model explore processes.

Language: Английский

---

Central Nervous System Targets: Inhibitory Interneurons in the Spinal Cord

Neurotherapeutics, Journal Year: 2020, Volume and Issue: 17(3), P. 874 - 885

Published: July 1, 2020

Pain is a percept of critical importance to our daily survival. In most cases, it serves both an adaptive function by helping us respond appropriately in potentially hostile environment and also protective role alerting tissue damage. Normally, evoked the activation peripheral nociceptive nerve endings subsequent relay information distinct cortical sub-cortical regions, but under pathological conditions that result chronic pain, can become spontaneous. Given one three pain patients do not treatments currently available, need for more effective analgesics evident. Two principal obstacles development novel analgesic therapies are limited understanding how neuronal circuits comprise these pathways transmit modulate sensory normal circumstances change leading states. this review, we focus on inhibitory interneurons setting thresholds and, particular, disinhibition spinal dorsal horn lead aberrant processing associated with

Language: Английский

---

Mediators of Neuropathic Pain; Focus on Spinal Microglia, CSF-1, BDNF, CCL21, TNF-α, Wnt Ligands, and Interleukin 1β

Frontiers in Pain Research, Journal Year: 2021, Volume and Issue: 2

Published: Aug. 25, 2021

Intractable neuropathic pain is a frequent consequence of nerve injury or disease. When peripheral nerves are injured, damaged axons undergo Wallerian degeneration. Schwann cells, mast fibroblasts, keratinocytes and epithelial cells activated leading to the generation an "inflammatory soup" containing cytokines, chemokines growth factors. These primary mediators sensitize sensory endings, attract macrophages, neutrophils lymphocytes, alter gene expression, promote post-translational modification proteins, ion channel function in afferent neurons. This leads increased excitability spontaneous activity secondary including colony stimulating factor 1 (CSF-1), chemokine C-C motif ligand 21 (CCL-21), Wnt3a, Wnt5a. Release these from neurons alters properties spinal microglial causing them release tertiary mediators, many situations

Language: Английский

---

Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization

Molecular Pain, Journal Year: 2021, Volume and Issue: 17

Published: Jan. 1, 2021

Microglia activation and subsequent pro-inflammatory responses play a key role in the development of neuropathic pain. The process microglia polarization towards phenotype often occurs during neuroinflammation. Recent studies have demonstrated an active for gut microbiota promoting microglial full maturation inflammatory capabilities via production Short-Chain Fatty Acids (SCFAs). However, it remains unclear whether SCFAs is involved pro-inflammatory/anti-inflammatory phenotypes In present study, chronic constriction injury (CCI) was used to induce pain mice, mechanical withdrawal threshold, thermal hyperalgesia were accomplished. levels markers including ionized calcium-binding adaptor molecule 1 (Iba1), cluster differentiation 11b (CD11b), CD68, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), anti-inflammatory CD206, IL-4 hippocampus spinal cord determined on day 21 after CCI. results showed that CCI produced allodynia hyperalgesia, also increased expressions (Iba1, CD11b) (CD68, IL-1β, TNF-α), but not marker (CD206, IL-4) cord, accompanied by gut. Notably, antibiotic administration reversed these abnormalities, its effects bloked administration. conclusion, data from our study suggest can lead while pathogenesis regulating polarization. Antibiotic may be new treatment reducing further inhibiting

Language: Английский

---

Neuropathic pain; what we know and what we should do about it

Frontiers in Pain Research, Journal Year: 2023, Volume and Issue: 4

Published: Sept. 22, 2023

Neuropathic pain can result from injury to, or disease of the nervous system. It is notoriously difficult to treat. Peripheral nerve promotes Schwann cell activation and invasion immunocompetent cells into site injury, spinal cord higher sensory structures such as thalamus cingulate cortices. Various cytokines, chemokines, growth factors, monoamines neuropeptides effect two-way signalling between neurons, glia immune cells. This sustained hyperexcitability spontaneous activity in primary afferents that crucial for onset persistence well misprocessing information supraspinal structures. Much current understanding aetiology identification drug targets derives studies consequences peripheral rodent models. Although a vast amount has been forthcoming, translation this clinical arena minimal. Few, if any, major therapeutic approaches have appeared since mid 1990's. may reflect failure recognise differences processing males vs. females, cellular responses different types humans animals. Basic science which seek bridge knowledge gap include better assessment animal models, use models emulate human disease, stratification phenotypes according quantitative signs symptoms disease. lead more personalized effective treatments individual patients. Significance statement: There an urgent need find new neuropathic pain. classical revealed essential features central sensitization some molecular mechanisms involved, they do not adequately model multiplicity states injuries bring forth clinic. review seeks integrate disciplines understand pain; including immunology, biology, electrophysiology biophysics, anatomy, neurology, pharmacology behavioral science. Beyond this, it underlines ongoing refinements basic practice will engender improved management.

Language: Английский

---