I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Objective
To present the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease.
Background
Although several diagnostic criteria for Parkinson9s disease have been proposed, none have been officially adopted by an official Parkinson society. Moreover, the commonest-used criteria, the UK brain bank, were created more than 25 years ago. In recognition of the lack of standard criteria, the MDS initiated a task force to design new diagnostic criteria for clinical Parkinson9s disease.
Methods/Results
The MDS-PD Criteria are intended for use in clinical research, but may also be used to guide clinical diagnosis. The benchmark is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise. Although motor abnormalities remain central, there is increasing recognition of non-motor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the MDS-PD Criteria retain motor parkinsonism as the core disease feature, defined as bradykinesia plus rest tremor and/or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies upon three categories of diagnostic features; absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of PD diagnosis). Two levels of certainty are delineated: Clinically-established PD (maximizing specificity at the expense of reduced sensitivity), and Probable PD (which balances sensitivity and specificity).
Conclusion
The MDS criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, criteria will need continuous revision to accommodate these advances. Disclosure: Dr. Postuma has received personal compensation for activities with Roche Diagnostics Corporation and Biotie Therapies. Dr. Berg has received research support from Michael J. Fox Foundation, the Bundesministerium fur Bildung und Forschung (BMBF), the German Parkinson Association and Novartis GmbH.

MDS Clinical Diagnostic Criteria for Parkinson's Disease (S19.001)

Superoxide dismutases (SODs) are universal enzymes of organisms that live in the presence of oxygen. They catalyze the conversion of superoxide into oxygen and hydrogen peroxide. Superoxide anions are the intended product of dedicated signaling enzymes as well as the byproduct of several metabolic processes including mitochondrial respiration. Through their activity, SOD enzymes control the levels of a variety of reactive oxygen species (ROS) and reactive nitrogen species, thus both limiting the potential toxicity of these molecules and controlling broad aspects of cellular life that are regulated by their signaling functions. All aerobic organisms have multiple SOD proteins targeted to different cellular and subcellular locations, reflecting the slow diffusion and multiple sources of their substrate superoxide. This compartmentalization also points to the need for fine local control of ROS signaling and to the possibility for ROS to signal between compartments. In this review, we discuss studies in model organisms and humans, which reveal the dual roles of SOD enzymes in controlling damage and regulating signaling.

/pdf/superoxide-dismutases-dual-roles-in-controlling-ros-damage-1o3hzqi1hc.pdf

Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling.

https://www.jstage.jst.go.jp/article/jjsth/26/1/26_17/_pdf

Seven-transmembrane receptors

Rare monogenic disorders of mitochondria have shed light on mitochondrial function, and the development of therapeutic agents for these disorders may be applicable to more common sporadic diseases characterized by mitochondrial dysfunction.

/pdf/monogenic-mitochondrial-disorders-2tobxroxud.pdf

Monogenic Mitochondrial Disorders

The dopaminergic system plays important roles in neuromodulation, such as motor control, motivation, reward, cognitive function, maternal, and reproductive behaviors. Dopamine is a neurotransmitter, synthesized in both central nervous system and the periphery, that exerts its actions upon binding to G protein-coupled receptors. Dopamine receptors are widely expressed in the body and function in both the peripheral and the central nervous systems. Dopaminergic signaling pathways are crucial to the maintenance of physiological processes and an unbalanced activity may lead to dysfunctions that are related to neurodegenerative diseases. Unveiling the neurobiology and the molecular mechanisms that underlie these illnesses may contribute to the development of new therapies that could promote a better quality of life for patients worldwide. In this review, we summarize the aspects of dopamine as a catecholaminergic neurotransmitter and discuss dopamine signaling pathways elicited through dopamine receptor activation in normal brain function. Furthermore, we describe the potential involvement of these signaling pathways in evoking the onset and progression of some diseases in the nervous system, such as Parkinson’s, Schizophrenia, Huntington’s, Attention Deficit and Hyperactivity Disorder, and Addiction. A brief description of new dopaminergic drugs recently approved and under development treatments for these ailments is also provided.

Dopamine: Functions, Signaling, and Association with Neurological Diseases

Mitochondrial compartmentalization of redox processes.

High fat diets and accompanying hepatic steatosis are highly prevalent conditions. Previous work has shown that steatosis is accompanied by enhanced generation of reactive oxygen species (ROS), which may mediate further liver damage. Here we investigated mechanisms leading to enhanced ROS generation following high fat diets (HFD). We found that mitochondria from HFD livers present no differences in maximal respiratory rates and coupling, but generate more ROS specifically when fatty acids are used as substrates. Indeed, many acyl-CoA dehydrogenase isoforms were found to be more highly expressed in HFD livers, although only the very long chain acyl-CoA dehydrogenase (VLCAD) was more functionally active. Studies conducted with permeabilized mitochondria and different chain length acyl-CoA derivatives suggest that VLCAD is also a source of ROS production in mitochondria of HFD animals. This production is stimulated by the lack of NAD(+). Overall, our studies uncover VLCAD as a novel, diet-sensitive, source of mitochondrial ROS.

/pdf/diet-sensitive-sources-of-reactive-oxygen-species-in-liver-56r4k69scd.pdf

Diet-sensitive sources of reactive oxygen species in liver mitochondria: role of very long chain acyl-CoA dehydrogenases.

Mitochondrial ion transport pathways: Role in metabolic diseases

Enhanced mitochondrial generation of oxidants, including hydrogen peroxide (H2O2), is related to a large number of pathological conditions, including diet-induced obesity and steatohepatosis. Indeed, we have previously shown that high fat diets increase the generation of H2O2 in liver mitochondria energized by activated fatty acids. Here, we further study fatty-acid induced H2O2 release in liver mitochondria, and determine the characteristics that regulate it. We find that this production of H2O2 is independent of mitochondrial inner membrane integrity and insensitive to purine nucleotides. On the other hand, palmitate-induced H2O2 production is strongly enhanced by high fat diets and is pH-sensitive, with a peak at a matrix pH of ~8.5. Using recombinantly expressed human very long chain acyl-CoA dehydrogenase, we are able to demonstrate that palmitate-induced H2O2 release may be ascribed to the activity of this enzyme alone, acting as an oxidase. Our results add to a number of findings indicating that sources outside of the electron transport chain can generate significant, physiopathologically relevant, amounts of oxidants in mitochondria.

Ariel R. Cardoso

Papers

Dopamine: Functions, Signaling, and Association with Neurological Diseases

Mitochondrial compartmentalization of redox processes.

Diet-sensitive sources of reactive oxygen species in liver mitochondria: role of very long chain acyl-CoA dehydrogenases.

Mitochondrial ion transport pathways: Role in metabolic diseases

H2O2 release from the very long chain acyl-CoA dehydrogenase.