Parkinson's disease; the hibernating spore hypothesis

The authors support the hypothesis that a causative agent in Parkinson's disease (PD) might be either fungus or bacteria with fungus-like properties - Actinobacteria, and that their spores may serve as 'infectious agents'. Updated research and the epidemiology of PD suggest that the disease might be induced by environmental factor(s), possibly with genetic susceptibility, and that α-synuclein probably should be regarded as part of the body's own defense mechanism. To explain the dual-hit theory with stage 1 involvement of the olfactory structures and the 'gut-brain'-axis, the environmental factor is probably airborne and quite 'robust' entering the body via the nose/mouth, then to be swallowed reaching the enteric nervous system with retained pathogenicity. Similar to the essence of smoking food, which is to eradicate microorganisms, a viable agent may be defused by tobacco smoke. Hence, the agent is likely to be a 'living' and not an inert agent. Furthermore, and accordant with the age-dependent incidence of LPD, this implies that a dormant viable agent have been escorted by α-synuclein via retrograde axonal transport from the nose and/or GI tract to hibernate in the associated cerebral nuclei. In the brain, PD spreads like a low-grade infection, and that patients develop symptoms in later life, indicate a relatively long incubation time. Importantly, Actinomyces species may form endospores, the hardiest known form of life on Earth. The authors hypothesize that certain spores may not be subject to degradation by macroautophagy, and that these spores become reactivated due to the age-dependent or genetic reduced macroautophagic function. Hence, the hibernating spore hypothesis explains both early-onset and late-onset PD. Evaluation of updated available information are all consistent with the hypothesis that PD may be induced by spores from fungi or Actinobacteria and thus supports Broxmeyer's hypothesis put forward 15 years ago.