Special issue “Parkinson’s disease”

Nuclear Factor-κB Dysregulation and α-Synuclein Pathology: Critical Interplay in the Pathogenesis of Parkinson’s Disease

“…The capability of pathological forms of α-syn to spread seems to be corroborated by neuropathological examination of post-mortem brains from patients who received fetal neuron grafts over one decade prior to death and showing the development of LB within grafted neuronal cells (Kordower et al, 2008a,b;Chu and Kordower, 2010;Li et al, 2010;Kurowska et al, 2011). These findings, together with the Braak hypothesis, suggesting that the progression of PD symptoms relates with the caudo-rostral diffusion of LB pathology in the brain (Braak et al, 2003(Braak et al, , 2018, fed the shoot up of the prionlike hypothesis of PD, emphasizing the multiple similarities between α-syn and prion protein (Olanow and Brundin, 2013;Brundin et al, 2016;Brundin and Melki, 2017). However, studies showing that PD patients exhibit a systemic α-syn neuropathology within both PNS and CNS (Gelpi et al, 2014;Surguchov, 2016) and a critical analysis of neuronal vulnerability to α-syn accumulation, were supportive for the development of alternative hypotheses as presented by Engelender and Isacson (2017) and Surmeier et al (2017).…”

Analytic Philosophy for Biomedical Research: The Imperative of Applying Yesterday’s Timeless Messages to Today’s Impasses

“…In the case of type 1 diabetes, in addition to the important issue of access to insulin, Linda DiMeglio and colleagues note that "clinicians, investigators, and patients have gained a better appreciation of the true complexity of type 1 diabetes, and humility in the face of many unsuccessful trials aimed at inducing a durable disease remission" [13]. In the field of Parkinson's disease research, Heiko Braak and co-authors write that "despite remarkable progress in the management of its motor symptoms by pharmacologic dopamine replacement or deep brain stimulation, there is still no cure and all attempts to develop treatments that halt or slow down the relentless progression of the disease have so far failed" [14]. A similar diagnosis can be said of Alzheimer's disease (AD) research.…”

“…13 In the Generation of Animals (GA), Aristotle makes an important distinction between the potential and the actual, stating that "all three kinds of soul [nutritive, sensitive and rational] …must be possessed potentially before they are possessed in actuality" (GA II.3). 14 In De Anima (On the Soul) III.5, he explains this notion to a greater extent, writing that "in a sense light makes potential colours into actual colours". 15 Connell provides a further helpful example from Metaphysics IX.7: "is earth potentially a human being?…”

“…Although beyond the purview of our present discussion, I think it is important to mention that reading the GA with an eye on epigenetic development [64] should always be accompanied by the determinants of "scope and limit": A fish embryo, although susceptible to certain variations, cannot naturally develop into a bird, or another species: a scope comes hand-in-hand with limits, and therefore epigenetic variation in development is considerably constrained. 16 10 From the Greek maieutikos "acting as midwife" 11 The Sophist translations are from Christopher Rowe's edition [59] 12 From William Ogle's translation (1882) (classics.mit.edu/Aristotle/parts_animals.html) 13 There are commonalities here with John Stuart Mill's 'method of difference' (A System of Logic, Ratiocinative and Inductive, 1843) 14 From Arthur Platt's translation (1910) (en.wikisource.org/wiki/On_the_Generation_of_Animals) 15 From J. A. Smith's translation (1931) (classics.mit.edu/Aristotle/soul.3.iii.html) 16 Noam Chomsky made a very pertinent comment related to this point in 1983: "Consider something that everybody agrees is due to heredity-the fact that humans develop arms rather than wings.…”

Design, synthesis, and in vitro evaluation of quinolinyl analogues for α-synuclein aggregation

“…5 Furthermore, Braak staging of brain tissue from PD cases suggests that the appearance of α -synuclein inclusions precedes dopaminergic loss 6 and that α -synuclein deposition may occur years prior to the appearance of motor symptoms. 7, 8 An additional concern is that treatment of PD with dopaminergic drugs alters the striatal uptake of dopaminergic imaging biomarkers used for monitoring disease progression; 9 poor correlation has been reported between PET measures with these tracers and clinical status in therapeutic trials of PD progression. 10, 11 Therefore, the strategy of imaging deposited α -synuclein aggregates rather than dopaminergic changes could provide a more accurate definition of early-stage premotor PD.…”