Future Neurology[JOURNAL]
Sun
105 papers
Autophagy in neuroprotection and neurodegeneration: A question of balance.
Cherra SJ, Chu CT
Future Neurol · 2008 May · PMID 18806889 · Full text
A central issue in developing therapies for neurodegenerative diseases involves understanding why adaptive responses to stress or injury fail to prevent synaptic dysfunction and neuronal cell death. Macroautophagy is a m...
A central issue in developing therapies for neurodegenerative diseases involves understanding why adaptive responses to stress or injury fail to prevent synaptic dysfunction and neuronal cell death. Macroautophagy is a major, evolutionarily conserved response to nutrient and bioenergetic stresses, which has the capacity to remove aggregated proteins and damaged organelles such as mitochondria. This has prompted intense interest in autophagy-related therapies for Huntington's, Alzheimer's, Parkinson's, stroke and other neurological diseases. However, excessive or imbalanced induction of autophagic recycling can actively contribute to neuronal atrophy, neurite degeneration and cell death. Oxidative-, aging- and disease-related increase in demand for autophagy, coupled with declining axonal trafficking, lysosomal degradation or biosynthetic efficiencies promote increased susceptibility to a harmful state of autophagic stress. A more complete understanding of dysfunction along the entire spectrum of autophagic recycling, from autophagosome formation through clearance and regeneration of new cellular components is necessary to restore balance to the system, promote neuronal health and maximize therapeutic potentials.
The Implications of the Cancer Stem Cell Hypothesis for Neuro-Oncology and Neurology.
Rich JN
Future Neurol · 2008 May · PMID 19763280 · Full text
The cancer stem cell hypothesis posits that cancers contain a subset of neoplastic cells that propagate and maintain tumors through sustained self-renewal and potent tumorigenecity. Recent excitement has been generated b...
The cancer stem cell hypothesis posits that cancers contain a subset of neoplastic cells that propagate and maintain tumors through sustained self-renewal and potent tumorigenecity. Recent excitement has been generated by a number of reports that have demonstrated the existence of cancer stem cells in several types of brain tumors. Brain cancer stem cells - also called tumor initiating cells or tumor propagating cells - share features with normal neural stem cells but do not necessarily originate from stem cells. Although most cancers have only a small fraction of cancer stem cells, these tumor cells have been shown in laboratory studies to contribute to therapeutic resistance, formation of new blood vessels to supply the tumor, and tumor spread. As malignant brain tumors rank among the deadliest of all neurologic diseases, the identification of new cellular targets may have profound implications in neuro-oncology. Novel drugs that target stem cell pathways active in brain tumors have been efficacious against cancer stem cells suggesting that anti-cancer stem cell therapies may advance brain tumor therapy. The cancer stem cell hypothesis may have several implications for other neurologic diseases as caution must be exercised in activating stem cell maintenance pathways in cellular therapies for neurodegenerative diseases. The ability for a small fraction of cells to determine the overall course of a disease may also inform new paradigms of disease that may translate into improved patient outcomes.
Therapeutic potential of statins in multiple sclerosis: immune modulation, neuroprotection and neurorepair.
Markovic-Plese S, Singh AK, Singh I
Future Neurol · 2008 Mar · PMID 20107624 · Full text
Statins as inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A reductase are widely used as cholesterol-lowering drugs. Recent studies provide evidence that the anti-inflammatory activity of statins, which is independen...
Statins as inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A reductase are widely used as cholesterol-lowering drugs. Recent studies provide evidence that the anti-inflammatory activity of statins, which is independent of their cholesterol-lowering effects, may have potential therapeutic implications for neuroinflammatory diseases such as multiple sclerosis (MS), Alzheimer's disease and brain tumors, as well as traumatic spinal cord and brain injuries. Studies with animal models of MS suggest that, in addition to immunomodulatory activities similar to the ones observed with approved MS medications, statin treatment also protects the BBB, protects against neurodegeneration and may also promote neurorepair. Although the initial human studies on statin treatment for MS are encouraging, prospective randomized clinical studies will be required to evaluate their efficacy in the larger patient population.
Experience--a double edged sword for restorative neural plasticity after brain damage.
Allred RP, Jones TA
Future Neurol · 2008 Mar · PMID 19718283 · Full text
During the time period following damage, the brain undergoes widespread reorganizational processes. Manipulations of behavioral experience can be potent therapeutic interventions for shaping this reorganization and enhan...
During the time period following damage, the brain undergoes widespread reorganizational processes. Manipulations of behavioral experience can be potent therapeutic interventions for shaping this reorganization and enhancing long-term functional outcome. Recovery of function is a major concern for survivors of central nervous system damage and management of post-injury rehabilitation is increasingly becoming a topic of chief importance. Animal research, the focus of this review, suggests that, in the absence of behavioral manipulations, the brain is unlikely to realize its full potential for supporting function. However, experiences also have the capacity to be maladaptive for brain and behavioral function. From a treatment perspective, it may be unwise to adopt the canon of "first, do no harm" because maladaptive experiences include behaviors that individuals learn to do on their own. A better understanding of how behavioral experience interacts with brain reorganization could result in rehabilitative therapies, individually tailored and optimized for functional outcome.
Inherited disorders of GABA metabolism.
Pearl PL, Hartka TR, Cabalza JL … +2 more , Taylor J, Gibson MK
Future Neurol · 2006 Sep · PMID 23842532 · Full text
The inherited disorders of γ-amino butyric acid (GABA) metabolism require an increased index of clinical suspicion. The known genetic disorders are GABA-transaminase deficiency, succinic semialdehyde dehydrogenase (SSADH...
The inherited disorders of γ-amino butyric acid (GABA) metabolism require an increased index of clinical suspicion. The known genetic disorders are GABA-transaminase deficiency, succinic semialdehyde dehydrogenase (SSADH) deficiency and homocarnosinosis. A recent link has also been made between impaired GABA synthesis and nonsyndromic cleft lip, with or without cleft palate. SSADH deficiency is the most commonly occurring of the inherited disorders of neurotransmitters. The disorder has a nonspecific phenotype with myriad neurological and psychiatric manifestations, and usually has a nonprogressive temporal course. Diagnosis is made by the detection of γ-hydroxybutyrate excretion on urine organic acid testing. The most consistent magnetic resonance imaging abnormality is an increased signal in the globus pallidus. Magnetic resonance spectroscopy has demonstrated the first example of increased endogenous GABA in human brain parenchyma in this disorder. GABA-transaminase deficiency and homocarnosinosis appear to be very rare, but require cerebrospinal fluid for detection, thus allowing for the possibility that these entities, as in the other inherited neurotransmitter disorders, are under-recognized.
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