Research has shown that mutant proteins bind to the CMA-pathway receptors on lysosomal membrane and in doing so block their own degradation as well as the degradation of other substrates. Membrane damage
Damage to the membranes of organelles by monomeric or oligomeric proteins could also contribute to these diseases. Alpha-synuclein can damage membranes by inducing membrane curvature, and cause extensive tubulation and vesiculation when incubated with artificial phospholipid vesicles.The tubes formed from these lipid vesicles consist of both micellar as well as bilayer tubes. Extensive induction of membrane curvature is deleterious to the cell and would eventually lead to cell death. Apart from tubular structures, alpha-synuclein can also form lipoprotein nanoparticles similar to apolipoproteins. Mitochondrial dysfunction
The most common form of cell death in neurodegeneration is through the intrinsic mitochondrial apoptotic pathway. This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial intermembrane space. Reactive oxygen species (ROS) are normal byproducts of mitochondrial respiratory chain activity. ROS concentration is mediated by mitochondrial antioxidants such as manganese superoxide dismutase (SOD2) and glutathione peroxidase. Over production of ROS (oxidative stress) is a central feature of all neurodegenerative disorders. In addition to the generation of ROS, mitochondria are also involved with life-sustaining functions including calcium homeostasis, PCD, mitochondrial fission and fusion, lipid concentration of the mitochondrial membranes, and the mitochondrial permeability transition.
Despite their popularity, antioxidant treatments have not been found to be effective medications for prevention of AMS. Interest in phosphodiesterase inhibitors such as sildenafil has been limited by the possibility that these drugs might worsen the headache of mountain sickness. A promising possible preventive for altitude sickness is myo-inositol trispyrophosphate (ITPP), which increases the amount of oxygen released by hemoglobin. Prior to the onset of altitude sickness, ibuprofen is a suggested non-steroidal anti-inflammatory and painkiller that can help alleviate both the headache and nausea associated with AMS. It has not been studied for the prevention of cerebral edema (swelling of the brain) associated with extreme symptoms of AMS. Over-the-counter herbal supplements and traditional medicines
Herbal supplements and traditional medicines are sometimes suggested to prevent high altitude sickness including ginkgo biloba, R crenulata, minerals such as iron, antacids, and hormonal-based supplements such as medroxyprogesterone and erythropoietin. Medical evidence to support the effectiveness and safety of these approaches is often contradictory or lacking. Indigenous peoples of the Americas, such as the Aymaras of the Altiplano, have for centuries chewed coca leaves to try to alleviate the symptoms of mild altitude sickness. This therapy has not yet been proven effective in a clinical study. In Chinese and Tibetan traditional medicine, an extract of the root tissue of Radix rhodiola is often taken in order to prevent the symptoms of high altitude sickness, however, no clear medical studies have confirmed the effectiveness or safety of this extract.