title: Neurodegenerative disorders share common features of "loss of function" states of a proposed mechanism of nervous system functions.
abstract: Neurodegenerative disorders are highly heterogeneous for the locations affected and the nature of the aggregated proteins. Nearly 80% of the neurodegenerative disorders occur sporadically, indicating that certain factors must combine to initiate the degenerative changes. The contiguous extension of degenerative changes from cell to cell, the association with viral fusion proteins, loss of dendritic spines (postsynaptic terminals), and the eventual degeneration of cells indicate the presence of a unique mechanism for inter-cellular spread of pathology. It is not known whether the "loss of function" states of the still unknown normal nervous system operations can lead to neurodegenerative disorders. Here, the possible loss of function states of a proposed normal nervous system function are examined. A reversible inter-postsynaptic functional LINK (IPL) mechanism, consisting of transient inter-postsynaptic membrane (IPM) hydration exclusion and partial to complete IPM hemifusions, was proposed as a critical step necessary for the binding process and the induction of internal sensations of higher brain functions. When various findings from different neurodegenerative disorders are systematically organized and examined, disease features match the effects of loss of function states of different IPLs. Changes in membrane composition, enlargement of dendritic spines by dopamine and viral fusion proteins are capable of altering the IPLs to form IPM fusion. The latter can lead to the observed lateral spread of pathology, inter-neuronal cytoplasmic content mixing and abnormal protein aggregation. Since both the normal mechanism of reversible IPM hydration exclusion and the pathological process of transient IPM fusion can evade detection, testing their occurrence may provide preventive and therapeutic opportunities for these disorders.
authors.affiliation: Neurosearch Center, 76 Henry Street, Toronto, ON, M5T1X2, Canada. Electronic address: kunjumon.vadakkan@utoronto.ca.
authors.forename: Kunjumon I
authors.initials: KI
authors.lastname: Vadakkan
mesh_terms: D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D008954:Models, Biological; D009420:Nervous System / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000473:pathology*
chemical_list: D008563:Membrane Lipids