Patients with Parkinson's disease showing symptoms of dyskinesia and depression, were found have autoantibodies including antineuronal-cells, anti-brain lysate, anti-dsDNA, anti-phosphatidylserine, anti-cardiolipin, anti-serotonin, and anti-melanocytes antibodies.
Reference:
Clin Rev Allergy Immunol. Immunology, Autoimmunity, and Autoantibodies in Parkinson's Disease.Benkler M
Salt-inducible kinase 2 (SIK2) reduced cAMP responsive elements binding protein (CREB). CREB is a protein that protects neurons after ischemia. Oxygen and glucose deprivation causes decreased CREB function. The study found neurons that lacked SIK2 had increased function after ischemia.
Reference:
Tsutomu Sasaki et al. SIK2 Is a Key Regulator for Neuronal Survival after Ischemia via TORC1-CREB. Neuron
New research has found that overproduction of Regulator of Calcineurin 1 (RCAN1), caused by stroke, hypertension or the presence of beta amyloid leads to neuronal atrophy in the hippocampus and cortex in people with Down Syndrome and Alzheimer's Disease.
Reference:
X. Sun, Y. Wu, B. Chen, Z. Zhang, W. Zhou, Y. Tong, J. Yuan, K. Xia, H. Gronemeyer, R. A. Flavell, W. Song. Regulator of calcineurin 1 (RCAN1) facilitates neuronal apoptosis through caspase 3 activation. Journal of Biological Chemistry
A new study has found that phosphoinositide kinases and calcium ions are important for proper neurobiological function. Changes in these molecules causes neurological and cardiovascular diseases, including stroke, epilepsy, dementia, hypertension.
Reference:
O. Zaika, J. Zhang, M. S. Shapiro. Combined Phosphoinositide and Ca2 Signals Mediating Receptor Specificity toward Neuronal Ca2 Channels. Journal of Biological Chemistry
More physical activity leads to less impairment of cognitive function and greater brain volume in the prefrontal cortex and temporal cortex. Walking increases your brain's resistance to the disease and reduce memory loss.
Reference:
SOURCE: Radiological Society of North America meeting, Nov. 29, 2010, news release.
Researchers are studying small molecules therapies which can stop Aβ42-fibrinogen interaction to prevent clot structures result in less oxygen to brain cells as a potential therapy for AD disease (a type of amyloid-β, called Aβ42, reacts with fibrinogen leading to oligomeric clots and deterioration of memory and cognitive ability).
References:
H. J. Ahn, D. Zamolodchikov, M. Cortes-Canteli, E. H. Norris, J. F. Glickman, S. Strickland. Alzheimer's disease peptide -amyloid interacts with fibrinogen and induces its oligomerization. Proceedings of the National Academy of Sciences,
The precuneus(a anatomical structure in the brain) develops amyloid deposits for patients with Alzheimer's disease and in pre-Alzheimer's . APOE4 is the major genetic risk factor for sporadic causes of developing Alzheimer's disease.
References:
Y. I. Sheline, J. C. Morris, A. Z. Snyder, J. L. Price, Z. Yan, G. D'Angelo, C. Liu, S. Dixit, T. Benzinger, A. Fagan, A. Goate, M. A. Mintun. APOE4 Allele Disrupts Resting State fMRI Connectivity in the Absence of Amyloid Plaques or Decreased CSF A 42. Journal of Neuroscience
A new research study has found that mutations in the progranulin gene (develops the progranulin protein and helps brain neurons), led to the development of frontotemporal lobar degeneration (FTLD) type of dementia. However, those individuals with a progranulin mutation who had copies of the protective TMEM106B allele did not develop FTLD immediately.
Reference:
N. Finch, M.M. Carrasquillo, M. Baker, N.J. Rutherford, G. Coppola, M. Dejesus-Hernandez, R. Crook, T. Hunter, R. Ghidoni, L. Benussi, J. Crook, E. Finger, K.J. Hantanpaa, A.M. Karydas, P. Sengdy, J. Gonzalez, W.W. Seeley, N. Johnson, T.G. Beach, M. Mesulam, G. Forloni, A. Kertesz, D.S. Knopman, R. Uitti, C.L. White III, R. Caselli, C. Lippa, E.H. Bigio, Z.K. Wszolek, G. Binetti, I.R. Mackenzie, B.L. Miller, B.F. Boeve, S.G. Younkin, D.W. Dickson, R.C. Petersen, N.R. Graff-Radford, D.H. Geschwind, R. Rademakers. TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers. Neurology,
Normally tau is a soluble protein. It’s function is to stabilize microtubules (polymers of α- and β-tubulin dimers). Hyperphosphorylation can cause loss of normal tau function and insoluble tau aggregates leading to cause frontotemporal lobar degeneration. Tau inclusions on histology are seen in Pick's disease, MAPT mutations, corticobasal degeneration, progressive supranuclear palsy.
Tau hyperphosphorylation reduces tau binding to microtubules and increases tau fibrillization. Currently, compounds that can stabilize microtubules; reduce tau hyperphosphorylation; inhibit tau formation of oligomers and fibrils; or enhance tau intracellular degradative pathways are under development to find cures for Alzheimer’s and other tauopathies.
Mutations in the LRRK2 gene, a protein that acts as a kinase, is a common cause of Parkinson’s disease. Researchers have discovered a broad spectrum of kinase inhibitors against LRRK2. For example, indolinones are the most effective at reducing LRRK2's kinase activity.
The parkin and PINK1 genes clear damaged mitochondria from the brain. These genes are not functioning optimally in patients with Parkinson’s disease. Moreover, genes for mitochondrial function are less active in people with Parkinson’s disease. Researchers are studying how PGC-1alpha, a gene that regulates energy metabolism and mitochondrial biogenesis( the production of new mitochondrion)
Lee, B.D. et al. "Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease." Nature Medicine, Vol. 16(9), pp. 998-1000
Zheng B et al. “PGC-1alpha, a potential therapeutic target for early intervention in Parkinson’s disease.” Science Translational Medicine, October 6, 2010, Vol. 2 (52), pp. 1-14
Researchers observed that if neuropeptide S receptors in the brain were activated immediately after a learning experience, it could be recalled for much longer and with much greater accuracy. The discovery could provide important clues about how the brain stores memories and also lead to new treatments for Alzheimer’s disease, dementia and other cognitive impairments.
Journal: Neuropeptide S Enhances Memory During the Consolidation Phase and Interacts with Noradrenergic Systems in the Brain
http://www.nature.com/npp/journal/vaop/ncurrent/full/npp2010207a.html
