2012. 2011. Neurodegeneration. Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons.
Many neurodegenerative diseases including ALS, Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many similarities appear that relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. There are many parallels between different neurodegenerative disorders including atypical protein assemblies as well as induced cell death. Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.
Links between neurodegenerative disorders Genetics Many neurodegenerative diseases are caused by genetic mutations, most of which are located in completely unrelated genes. Protein misfolding cytosol, e.g. European Federation of Neurological Associations. Blood-brain barrier. The astrocytes type 1 surrounding capillaries in the brain A cortical microvessel stained for blood–brain barrier protein ZO-1 The blood–brain barrier (BBB) is a highly selective permeability barrier that separates the circulating blood from the brain extracellular fluid (BECF) in the central nervous system (CNS).
The blood-brain barrier is formed by capillary endothelial cells, which are connected by tight junctions with an extremely high electrical resistance of at least 1000 Ωcm−2. The blood-brain barrier allows the passage of water, some gases, and lipid soluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids that are crucial to neural function. Adenosine. Adenosine (ADO) is a purine nucleoside comprising a molecule of adenine attached to a ribose sugar molecule (ribofuranose) moiety via a β-N9-glycosidic bond.
Adenosine plays an important role in biochemical processes, such as energy transfer — as adenosine triphosphate (ATP) and adenosine diphosphate (ADP) — as well as in signal transduction as cyclic adenosine monophosphate, cAMP. It is also an inhibitory neurotransmitter, believed to play a role in promoting sleep and suppressing arousal. Adenosine also plays a role in regulation of blood flow to various organs through vasodilation. Pharmacological effects Adenosine is an endogenous purine nucleoside that modulates many physiological processes. In the USA, Adenosine is marketed as Adenocard. Adenosine receptors All adenosine receptor subtypes (A1, A2A, A2B, and A3) are seven-transmembrane-spanning G-protein-coupled receptors. Anti-inflammatory properties A New Way To Breach The Blood-brain Barrier.
Breaching the blood-brain barrier: Researchers may have solved 100-year-old puzzle. Cornell University researchers may have solved a 100-year puzzle: How to safely open and close the blood-brain barrier so that therapies to treat Alzheimer's disease, multiple sclerosis and cancers of the central nervous system might effectively be delivered. (Journal of Neuroscience, Sept. 14, 2011.) The researchers found that adenosine, a molecule produced by the body, can modulate the entry of large molecules into the brain.
Engineers use short ultrasound pulses to reach neurons through blood-brain barrier. Columbia Engineering researchers have developed a new technique to reach neurons through the blood-brain barrier (BBB) and deliver drugs safely and noninvasively.
Up until now, scientists have thought that long ultrasound pulses, which can inflict collateral damage, were required. But in this new study, the Columbia Engineering team show that extremely short pulses of ultrasound waves can open the blood-brain barrier -- with the added advantages of safety and uniform molecular delivery -- and that the molecule injected systemically could reach and highlight the targeted neurons noninvasively. The study, led by Elisa Konofagou, associate professor of biomedical engineering and radiology, will be published in the online Early Edition of the Proceedings of the National Academy of Sciences the week of September 19, 2011. "This is a great step forward," says Konofagou. Highly specific delivery of drugs to human organs is essential for the effective treatment of many diseases.
Maybe You Do Need a Hole in Your Head - to Let the Medicine In. These days, researchers unraveling the workings of the brain’s filter are trying to find similar kinds of passageways so they can get drugs past it too.
Pardridge and his colleagues wondered if they could slip therapeutic compounds into the brain with the help of insulin and transferrin, a molecule that moves iron from place to place; both insulin and transferrin are granted free passage across the blood-brain barrier. To turn ordinary insulin and transferrin into Trojan Horses that can sneak other molecules inside, they engineered antibodies that could grab onto them. Next they welded drugs onto the antibodies. In one experiment last year, the team attached erythropoietin, a compound that can help heal injured cells. They then injected the antibody-erythropoietin combination into the bloodstream of mice. In May researchers at the biotech company Genentech unveiled another way to trick the brain into letting down its guard.