One of the common neurological complications in patients with the acquired immune deficiency syndrome (AIDS) is a subacute encephalopathy with progressive dementia. By using the techniques of cocultivation for virus isolation, in situ hybridization, immunocytochemistry, and transmission electron microscopy, the identity of an important cell type that supports replication of the AIDS retrovirus in brain tissue was determined in two affected individuals. These cells were mononucleated and multinucleated macrophages that actively synthesized viral RNA and produced progeny virions in the brains of the patients. Infected brain macrophages may serve as a reservoir for virus and as a vehicle for viral dissemination in the infected host.

https://science.sciencemag.org/content/sci/233/4768/1089.full.pdf

Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy.

Most cancer cells exhibit increased glycolysis and use this metabolic pathway for generation of ATP as a main source of their energy supply. This phenomenon is known as the Warburg effect and is considered as one of the most fundamental metabolic alterations during malignant transformation. In recent years, there are significant progresses in our understanding of the underlying mechanisms and the potential therapeutic implications. Biochemical and molecular studies suggest several possible mechanisms by which this metabolic alteration may evolve during cancer development. These mechanisms include mitochondrial defects and malfunction, adaptation to hypoxic tumor microenvironment, oncogenic signaling, and abnormal expression of metabolic enzymes. Importantly, the increased dependence of cancer cells on glycolytic pathway for ATP generation provides a biochemical basis for the design of therapeutic strategies to preferentially kill cancer cells by pharmacological inhibition of glycolysis. Several small molecules have emerged that exhibit promising anticancer activity in vitro and in vivo, as single agent or in combination with other therapeutic modalities. The glycolytic inhibitors are particularly effective against cancer cells with mitochondrial defects or under hypoxic conditions, which are frequently associated with cellular resistance to conventional anticancer drugs and radiation therapy. Because increased aerobic glycolysis is commonly seen in a wide spectrum of human cancers and hypoxia is present in most tumor microenvironment, development of novel glycolytic inhibitors as a new class of anticancer agents is likely to have broad therapeutic applications.

/pdf/glycolysis-inhibition-for-anticancer-treatment-40rjcq29jf.pdf

Glycolysis inhibition for anticancer treatment

Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects.

The major inhibitory neurotransmitter in mammalian brain, y-aminobutyric acid (GABA), exerts its effects through increased postsynaptic membrane permeability to chloride ions (McBurney and Barker, 1978; Nistri et a]., 1980). The GABA receptor and associated chloride ion channel appear to be part of a protein complex containing receptor sites for GABA, benzodiazepines, and picrotoxininl barbiturates, as well as the chloride ionophore (Fig. 1). The three types of drug receptor sites studied by radioactive ligand binding have been thoroughly characterized to show their relevance to in vivo actions of the drugs that bind to the receptor sites in v i m . Various lines of evidence support the hypothesis that modulation of the postsynaptic response to GABA is involved in many of the actions of both the benzodiazepines (Haefely et a]., 1979; Costa and Guidotti, 1979) and the barbiturates and related central nervous system depressants (Nicoll et al., 1975; Haefely et a]., 1979; Macdonald and Barker, 1979). This article reviews the recent evidence for in v i m interactions between the three categories of drug receptors; the evidence supports the model for a complex as depicted in Fig. 1 and thus the relevance of GABA to the actions of the other drugs.

GABA‐Benzodiazepine‐Barbiturate Receptor Interactions

Publisher Summary This chapter presents an overview of PC12 pheochromocytoma cultures in neurobiological research. The PC12 line of rat pheochromocytoma cells promises to be highly useful for studying both chromaffin cells and neurons and, consequently, has been employed in an increasing number of laboratories. PC12 cells propagated in vivo or in culture without nerve-growth factor are readily classifiable as pheochromocytomas by current morphological and chemical criteria. They have no processes and are characterized by numerous secretory granules ranging in diameter up to 350 nm. They also contain total catecholamine stores comparable to those in rat adrenal glands and show intense formaldehyde-induced fluorescence. In addition to catecholamines, PC12 cells contain several other secretory products, some of which have also been reported in human pheochromocytomas. The morphology of the cells and their synthesis, storage, release, and uptake of neurohumoral or neurotransmitter substances can be modulated in a number of ways within the overall chromaffin cell-like phenotype. This chapter reviews the currently known properties of the PC12 line. It also discusses the ways in which it has been and could be exploited to increase the knowledge of neuronal and neurosecretory cells.

PC12 Pheochromocytoma Cultures in Neurobiological Research

Four double antibody solid-phase radioimmunoassay systems are described for the measurement of neuron-specific enolase (NSE) and non-neuronal enolase (NNE) from rat, monkey and human brain tissue. NSE and NNE are antigenically distinct, making their respective assays specific. The levels of neuronal and non-neuronal enolase (an enolase recently shown to be localized in glial cells) are determined in various regions of rat, monkey and human nervous system. Both neuronal and glial enolases are major proteins of brain tissue with each representing about 1.5% of total brain soluble protein. NSE levels are highest and NNE levels lowest in brain areas having a high proportion of grey matter, such as the cerebral cortex. The reverse is true for areas high in white matter, such as the pyramidal tract and the corpus callosum. Peripheral nervous system levels of NSE are much lower than those of brain with the spinal cord intermediate between the two.



Radioimmunological and immunocytochemical data show that neuron-specific enolase is also present in neuroendocrine cells located in non-nervous tissue, which include pinealocytes, parafollicular cells of the thyroid, adrenal medullary chromaffin cells, glandular cells of the pituitary and Islet of Langerhans cells in the pancreas. Unlike neurons, these cells also contain non-neuronal enolase in high amounts.

Alexandra M. Parma

Papers

Measurement of neuron-specific (NSE) and non-neuronal (NNE) isoenzymes of enolase in rat, monkey and human nervous tissue.

Developmental profile of neuron-specific (NSE) and non-neuronal (NNE) enolase

Purinergic inhibition of diazepam binding to rat brain (in vitro).

Chronic caffeine consumption increases the number of brain adenosine receptors.

Specific and potent interactions of carbamazepine with brain adenosine receptors.