Abstract:
:Temozolomide (TMZ), an oral alkylating prodrug which delivers a methyl group to purine bases of DNA (O6- guanine; N7-guanine and N3-adenine), is frequently used together with radiotherapy as part of the first-line treatment of high-grade gliomas. The main advantages are its high oral bioavailability (almost 100% although the concentration found in the cerebrospinal fluid was approximately 20% of the plasma concentration of TMZ), its lipophilic properties, and small size that confer the ability to cross the blood-brain barrier. Furthermore, this agent has demonstrated activity not only in brain tumors but also in a variety of solid tumors. However, conventional therapy using surgery, radiation, and TMZ in glioblastoma results in a median patient survival of 14.6 months. Treatment failure has been associated with the tumor drug resistance. This phenomenon has been linked to the expression of O6-methylguanine-DNA methyltransferase, but the mismatch repair system and the presence of cancer stem-like cells in tumors have also been related to TMZ resistance. The understanding of these mechanisms is essential for the development of new therapeutic strategies in the clinical use of TMZ, including the use of nanomaterial delivery systems and the association with other chemotherapy agents. The aim of this review is to summarize the resistance mechanisms of TMZ and the current advances to improve its clinical use.
journal_name
Curr Neuropharmacoljournal_title
Current neuropharmacologyauthors
Ortiz R,Perazzoli G,Cabeza L,Jiménez-Luna C,Luque R,Prados J,Melguizo Cdoi
10.2174/1570159X18666200626204005subject
Has Abstractpub_date
2020-06-26 00:00:00eissn
1570-159Xissn
1875-6190pii
CN-EPUB-107689pub_type
杂志文章abstract::Autophagy is a cellular quality control mechanism crucial for neuronal homeostasis. Defects in autophagy are critically associated with mechanisms underlying Parkinson's disease (PD), a common and debilitating neurodegenerative disorder. Autophagic dysfunction in PD can occur at several stages of the autophagy/lysosom...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159x13666151030103027
更新日期:2016-01-01 00:00:00
abstract::Brain and spinal cord injuries present significant therapeutic challenges. The treatments available for these conditions are largely ineffective, partly due to limitations in directly targeting the therapeutic agents to sites of pathology within the central nervous system (CNS). The use of stem cells to treat these co...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/157015910793358204
更新日期:2010-12-01 00:00:00
abstract::Depression is a serious psychiatric illness that affects millions of people worldwide. Weeks of antidepressant therapy are required to relieve depressive symptoms, and new drugs are still being extensively researched. The latest studies have shown that in depression, there is an imbalance between the main excitatory (...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159x13666150115220617
更新日期:2015-01-01 00:00:00
abstract::It has been well established that there is a connection between type II diabetes (DMTII) and Alzheimer's disease (AD). In fact, the increase in AD incidence may be an emerging complication of DMTII. Both pathologies are related to estradiol (E2) exposure on the one hand, estrogen receptors (ER) are emerging as importa...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/1570159X18666201111103024
更新日期:2020-11-10 00:00:00
abstract:BACKGROUND:Shared connections between physical activity and neuroprotection have been studied for decades, but the mechanisms underlying this effect of specific exercise were only recently brought to light. Several evidences suggest that physical activity may be a reasonable and beneficial method to improve functional ...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159X14666160330105132
更新日期:2017-01-01 00:00:00
abstract::Changes of the tumor necrosis factor-alpha (TNF-alpha) system have been shown to be involved in the development of psychiatric disorders and are additionally associated with changes in body weight as well as endocrine and metabolic changes in psychiatric patients. TNF-alpha might, for example, contribute to the pathog...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/157015908785777238
更新日期:2008-09-01 00:00:00
abstract::Liver failure can lead to generalized hyperammonemia, which is thought to be the underlying cause of hepatic encephalopathy. This neuropsychiatric syndrome is accompanied by functional changes of astrocytes. These glial cells enter ammonia-induced self-amplifying cycle characterized by brain oedema, oxidative and osmo...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/1570159X12666140903094700
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND:Depression is among the commonest of psychiatric disorders, and inflammatory mechanisms have been suggested to play a role in its pathophysiology. Interferons are a superfamily of proinflammatory cytokines that play a role in host defence mechanisms. Interferons are used in the treatment of a variety of auto...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159x14666160106155129
更新日期:2016-01-01 00:00:00
abstract::Neurodegeneration is an initial process in the development of diabetic retinopathy (DR). High quantities of glutamate, oxidative stress, induction of the renin-angiotensin system (RAS) and elevated levels of RAGE are crucial elements in the retinal neurodegeneration caused by diabetes mellitus. At least, there is emer...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159x14666160813182009
更新日期:2016-01-01 00:00:00
abstract::Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stres...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/1570159X11666131120224653
更新日期:2014-03-01 00:00:00
abstract::Ketamine is a noncompetitive antagonist of the NMDA-receptors, used as a dissociative anesthetic, presently included in the category of the psychoactive substances known as "club drugs". Ketamine administration was associated with impaired working memory and increased psychopathological symptoms, but there is a lack o...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/157015911795016912
更新日期:2011-03-01 00:00:00
abstract::The calcium (Ca(2+))-sensing receptor (CaR) belongs to family C of the G-protein coupled receptors (GPCRs). The receptor is activated by physiological levels of Ca(2+) (and Mg(2+)) and positively modulated by a range of proteinogenic L-alpha-amino acids. Recently, several synthetic allosteric modulators of the recepto...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/157015907781695982
更新日期:2007-09-01 00:00:00
abstract::As acetylcholinesterase (AChE) inhibitors are an important therapeutic strategy in Alzheimer's disease, efforts are being made in search of new molecules with anti-AChE activity. The fact that naturally-occurring compounds from plants are considered to be a potential source of new inhibitors has led to the discovery o...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/1570159X11311040004
更新日期:2013-07-01 00:00:00
abstract::Alzheimer's disease is one of the most progressive forms of dementia, ultimately leading to death in aged populations. The major hallmarks of Alzheimer's disease include deposition of extracellular amyloid senile plaques and intracellular neurofibrillary tangles in brain neuronal cells. Although there are classical th...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/1570159X18666200128121920
更新日期:2020-01-01 00:00:00
abstract::Protein aggregates or inclusion bodies are common hallmarks of age-related neurodegenerative disorders. Why these aggregates form remains unclear. Equally debated is whether they are toxic, protective, or simple by-products. Increasing evidence, however, supports the notion that in general aggregates confer toxicity a...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/157015908784533897
更新日期:2008-06-01 00:00:00
abstract::During the last decade, several meta-analytic studies employing different methodological approaches have had inconsistent conclusions regarding antidepressant efficacy. Herein, we aim to comment on methodological aspects that may have contributed to disparate findings. We initially discuss methodological inconsistenci...
journal_title:Current neuropharmacology
pub_type: 杂志文章,meta分析
doi:10.2174/1570159x13666150630174343
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Both prescription and over-the-counter (OTC) drugs recently emerged among novel psychoactive substances (NPS) being reported as ingested for recreational purposes. Among them, benzydamine (BZY), normally prescribed as an OTC anti-inflammatory drug, is reportedly being diverted and recreationally used. OBJEC...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/1570159X19666210113151136
更新日期:2021-01-13 00:00:00
abstract::Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and associated with high levels of morbidity and disability and with a great risk of suicide. While there is a general consensus on the symptomatology of depressio...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159X14666160607100403
更新日期:2017-04-01 00:00:00
abstract::Ion channels are complex transmembrane proteins that orchestrate the electrical signals necessary for normal function of excitable tissues, including the central nervous system, peripheral nerve, and both skeletal and cardiac muscle. Progress in molecular biology has allowed cloning and expression of genes that encode...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/157015911796557966
更新日期:2011-09-01 00:00:00
abstract::Mammalian STE20-like kinase-1 (Mst1) is a generally expressed apoptosis-promoting kinase and a key bridgebuilder of apoptotic signaling in the etiology of tissue injury. Despite the fact that the biological function of Mst1 and its role in the cell's signalling network have yet to be determined, however, there is a lo...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159X16666180516095949
更新日期:2018-01-01 00:00:00
abstract::Long-term potentiation (LTP) and long-term depression (LTD) are two distinct forms of synaptic plasticity that have been extensively characterized at the Schaffer collateral-CA1 (SCCA1) synapse and the mossy fiber (MF)-CA3 synapse within the hippocampus, and are postulated to be the molecular underpinning for several ...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159x13666150421003225
更新日期:2016-01-01 00:00:00
abstract::Over the last decades, the scientific interest in chemistry and pharmacology of cannabinoids has increased. Most attention has focused on ∆(9)-tetrahydrocannabinol (∆(9)-THC) as it is the psychoactive constituent of Cannabis sativa (C. sativa). However, in previous years, the focus of interest in the second plant cons...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/1570159X11666131204235805
更新日期:2014-05-01 00:00:00
abstract::Traumatic brain injury (TBI) is the principal cause of invalidity and death in the population under 45 years of age worldwide. This mini-review aims to systematize the forensic approach in neuropathological studies, highlighting the proper elements to be noted during external, radiological, autoptical, and histologica...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/1570159X17666191101123145
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Traumatic brain injury (TBI) constitutes the primary reason for mortality and morbidity in persons worldwide below 45 years of age. 1.7 million Traumatic events occur yearly in the United States alone, considering for 50,000 deaths. In severe traumatic brain injury sufferers, a considerable achievement attai...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159X15666170613083606
更新日期:2018-01-01 00:00:00
abstract::Malignant glioma is the most common and destructive form of primary brain tumor. Along with surgery and radiation, chemotherapy remains as the major treatment modality. The emergence of drug resistance, however, often leads to a therapeutic failure in the treatment of glioma, precluding long-term survival of the patie...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/157015912799362733
更新日期:2012-03-01 00:00:00
abstract::Neuronal nicotinic acetylcholine receptors (nAChRs) belong to a super-family of Cysloop ligand-gated ion channels that respond to endogenous acetylcholine (ACh) or other cholinergic ligands. These receptors are also the targets of drugs such as nicotine (the main addictive agent delivered by cigarette smoke) and are i...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159X15666170912110450
更新日期:2018-01-01 00:00:00
abstract::Major depressive disorder (MDD) is estimated to impose maximum debilitating effects on the society by 2030, with its critical effects on health, functioning, quality of life and concomitant high levels of morbidity and mortality. Yet, the disease is inadequately understood, diagnosed and treated. Moreover, with the re...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159X17666191001142934
更新日期:2020-01-01 00:00:00
abstract::Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for ...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159x14666160223121002
更新日期:2017-01-01 00:00:00
abstract::It is well recognized the role of the Wnt pathway in many developmental processes such as neuronal maturation, migration, neuronal connectivity and synaptic formation. Growing evidence is also demonstrating its function in the mature brain where is associated with modulation of axonal remodeling, dendrite outgrowth, s...
journal_title:Current neuropharmacology
pub_type: 杂志文章
doi:10.2174/1570159X11311050001
更新日期:2013-09-01 00:00:00
abstract::The push-pull superfusion technique (PPST) is a procedure for in vivo examination of transmitter release in distinct brain areas. This technique allows to investigate dynamics of transmitter release both under normal and experimentally evoked conditions. The PPST can be modified so that it is possible to determine rel...
journal_title:Current neuropharmacology
pub_type: 杂志文章,评审
doi:10.2174/1570159x13666150722233149
更新日期:2015-01-01 00:00:00