PERSPECTIVES Small Heat Shock Proteins, Amyloid Fibrils, and Nicotine Stimulate a Common Immune Suppressive Pathway with Implications for Future Therapies

The α7 nicotinic acetylcholine receptor (α7nAChR) is central to the anti-inflammatory function of the vagus nerve in a physiological mechanism termed the inflammatory reflex. Studies on the inflammatory reflex have been instrumental for the current development of the field of bioelectronic medicine. An independent investigation of the biological role of αB-crystallin (HspB5), the most abundant gene transcript present in active multiple sclerosis lesions in human brains, also led to α7nAChR. Induction of experimental autoimmune encephalomyelitis (EAE) in HspB5–/– mice results in greater paralytic signs, increased levels of proinflammatory cytokines, and T-lymphocyte activation relative to wild-type animals. Administration of HspB5 was therapeutic in animal models of multiple sclerosis, retinal and cardiac ischemia, and stroke. Structure–activity studies established that residues 73–92 were as potent as the parent protein, but only when it formed amyloid fibrils. Amyloid fibrils and small heat shock proteins (sHsps) selectively bound α7nAChR on peritoneal macrophages (Ms) and B lymphocytes, converting the Ms to an immune suppressive phenotype and mobilizing the migration of both cell types from the peritoneum to secondary lymph organs. Here, we review multiple aspects of this work, which may be of interest for developing future therapeutic approaches for multiple sclerosis and other disorders.
Source: Cold Spring Harbor perspectives in medicine - Category: Research Authors: Tags: Bioelectronic Medicine PERSPECTIVES Source Type: research

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Abstract Purinergic signaling was proposed in 1972, after it was demonstrated that adenosine 5'-triphosphate (ATP) was a transmitter in nonadrenergic, noncholinergic inhibitory nerves supplying the guinea-pig taenia coli. Later, ATP was identified as an excitatory cotransmitter in sympathetic and parasympathetic nerves, and it is now apparent that ATP acts as a cotransmitter in most, if not all, nerves in both the peripheral nervous system and central nervous system (CNS). ATP acts as a short-term signaling molecule in neurotransmission, neuromodulation, and neurosecretion. It also has potent, long-term (trophic) ...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Methods Mol Biol Source Type: research
Discussion Facial nerve palsy has been known for centuries, but in 1821 unilateral facial nerve paralysis was described by Sir Charles Bell. Bell’s palsy (BP) is a unilateral, acute facial paralysis that is clinically diagnosed after other etiologies have been excluded by appropriate history, physical examination and/or laboratory testing or imaging. Symptoms include abnormal movement of facial nerve. It can be associated with changes in facial sensation, hearing, taste or excessive tearing. The right and left sides are equally affected but bilateral BP is rare (0.3%). Paralysis can be complete or incomplete at prese...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Conclusion To conclude, this study suggests a preserved plasticity in the skeletal muscle of a patient with MELAS. More importantly, Resistance Training appears to be a safe and effective method to increase skeletal muscle function in this patient population, and this effect is mediated by both neuromuscular and mitochondrial adaptations. However, particular attention and caution is needed in the interpretation of the data of this single case study and further studies are warranted including larger sample of patients. Ethics Statement For this case study the participant caregiver provided written informed consent. Auth...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusions and Perspectives In this review we have summarized the critical role phagocytosis plays in both CNS homeostasis and disease. While much progress has been made in recent years, many unanswered questions remain. How phagocytosis in the CNS is influenced by numerous factors, such as microenvironment or phagocytic target, have yet to be fully resolved. Additionally, the utilization of novel technologies, including in vivo imaging techniques (217), iPSC-derived microglia (213) and high-throughput screens (66), will likely contribute to further identification of phagocytic pathways and consequences of phagocytosis w...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroinfla...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
CONCLUSIONS: There are limited studies that have evaluated the cost-effectiveness of physiotherapy treatments in neurological disorders. Three studies that combined extra physiotherapy-by-physiotherapy assistant and novel interventions with conventional physiotherapy were found not cost-effective. Implications for Rehabilitation Progressive muscle strengthening exercise over a period of 6-month is reported to be cost-effective for falls prevention in people with Parkinson's disease Aerobic training is reported as potentially cost-effective for older adults with vascular cognitive impairment Physiotherapy given as an adjuva...
Source: Disability and Rehabilitation - Category: Rehabilitation Authors: Tags: Disabil Rehabil Source Type: research
Spasticity occurs frequently following lesions of central motor pathways in neurological disorders such as stroke (Malhotra et al., 2009; Sommerfeld et al., 2012), spinal cord injury (Sheean, 2002), multiple sclerosis (MS) (Sinkjaer et al., 1993; Mayer, 1997) and cerebral palsy (CP) (Gracies, 2005). Spasticity is most commonly defined as a velocity dependent increase in muscle tone with exaggeration of the stretch reflex circuitry (Lance, 1980). However, in the clinic a somewhat broader understanding of spasticity, which also includes sustained muscle contractions such as spasms and spastic dystonia as well as alterations ...
Source: Clinical Neurophysiology - Category: Neuroscience Authors: Source Type: research
ConclusionDespite high prevalence rates and important clinical implications, sexual dysfunction is not systematically assessed in women presenting various neurological conditions. Several well-validated tools exist for such assessments, which could be used for sexual rehabilitation in these patients. The implementation of systematic assessments of sexual potential is feasible and renewed efforts should be made to do so in clinical practice.
Source: Annals of Physical and Rehabilitation Medicine - Category: Rehabilitation Source Type: research
AbstractNeurological disorders, such as spinal cord injury, stroke, traumatic brain injury, cerebral palsy, and multiple sclerosis cause motor impairments that are a huge burden at the individual, family, and societal levels. Spinal reflex abnormalities contribute to these impairments. Spinal reflex measurements play important roles in characterizing and monitoring neurological disorders and their associated motor impairments, such as spasticity, which affects nearly half of those with neurological disorders. Spinal reflexes can also serve as therapeutic targets themselves. Operant conditioning protocols can target benefic...
Source: Neurotherapeutics - Category: Neurology Source Type: research
ConclusionDespite high prevalence rates and important clinical implications, sexual dysfunction is not systematically assessed in women presenting various neurological conditions. Several well-validated tools exist for such assessments, which could be used for sexual rehabilitation in these patients. The implementation of systematic assessments of sexual potential is feasible and renewed efforts should be made to do so in clinical practice.
Source: Annals of Physical and Rehabilitation Medicine - Category: Rehabilitation Source Type: research
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