Fritz Heinrich Lewy (1885–1950)

Holdorff, Bernd

doi:10.1007/s00415-006-0130-2

Cited by 19 publications

(15 citation statements)

References 4 publications

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“…16.1; Panel A). Lewy first described intraneuronal proteinaceous inclusions in 1912 where he identified them in brain sections from patients with idiopathic paralysis agitans (the history of the Lewy body is reviewed in (Holdorff 2006; Rodrigues e Silva et al 2010)). The Russian neuropathologist Konstantin Tretiakoff coined the term “corps de Lewy” to describe these inclusions in his thesis on the SN as a tribute to Lewy’s first observation (Rodrigues e Silva et al 2010).…”

Section: 3 Pathological Features Of Pdmentioning

confidence: 99%

Parkinson’s Disease

Mhyre¹,

Boyd²,

Hamill³

et al. 2012

Subcellular Biochemistry

347

203

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Parkinson’s disease (PD) is the most common age-related motoric neurodegenerative disease initially described in the 1800’s by James Parkinson as the ‘Shaking Palsy’. Loss of the neurotransmitter dopamine was recognized as underlying the pathophysiology of the motor dysfunction; subsequently discovery of dopamine replacement therapies brought substantial symptomatic benefit to PD patients. However, these therapies do not fully treat the clinical syndrome nor do they alter the natural history of this disorder motivating clinicians and researchers to further investigate the clinical phenotype, pathophysiology/pathobiology and etiology of this devastating disease. Although the exact cause of sporadic PD remains enigmatic studies of familial and rare toxicant forms of this disorder have laid the foundation for genome wide explorations and environmental studies. The combination of methodical clinical evaluation, systematic pathological studies and detailed genetic analyses have revealed that PD is a multifaceted disorder with a wide-range of clinical symptoms and pathology that include regions outside the dopamine system. One common thread in PD is the presence of intracytoplasmic inclusions that contain the protein, α-synuclein. The presence of toxic aggregated forms of α-synuclein (e.g., amyloid structures) are purported to be a harbinger of subsequent pathology. In fact, PD is both a cerebral amyloid disease and the most common synucleinopathy, that is, diseases that display accumulations of α-synuclein. Here we present our current understanding of PD etiology, pathology, clinical symptoms and therapeutic approaches with an emphasis on misfolded α-synuclein.

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Section: 3 Pathological Features Of Pdmentioning

confidence: 99%

Parkinson’s Disease

Mhyre¹,

Boyd²,

Hamill³

et al. 2012

Subcellular Biochemistry

347

203

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“…The subsequent loss of midbrain dopaminergic neurons of the substantia nigra, pars compacta, results in striatal dopaminergic denervation. An interesting fact is that Frederic Lewy first identified the eponymous Lewy body, of which α-synuclein fibrils are the structural component, not in the substantia nigra but in the nbM [24]. In the Braak temporal staging proposal of PD pathology, Lewy bodies and neuronal loss in the substantia nigra occurs concurrently with accumulation of α-synuclein deposition in cholinergic neurons of the BF [2].…”

Section: Introductionmentioning

confidence: 99%

Cholinergic Dysfunction in Parkinson’s Disease

Müller

Bohnen

2013

Curr Neurol Neurosci Rep

216

137

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There is increasing interest in the clinical effects of cholinergic basal forebrain and tegmental pedunculopontine complex (PPN) projection degeneration in Parkinson’s disease (PD). Recent evidence supports an expanded role beyond cognitive impairment, including effects on olfaction, mood, REM sleep behavior disorder, and motor functions. Cholinergic denervation is variable in PD without dementia and may contribute to clinical symptom heterogeneity. Early in vivo imaging evidence that impaired cholinergic integrity of the PPN associates with frequent falling in PD is now confirmed by human post-mortem evidence. Brainstem cholinergic lesioning studies in primates confirm the role of the PPN in mobility impairment. Degeneration of basal forebrain cholinergic projections correlates with decreased walking speed. Cumulatively, these findings provide evidence for a new paradigm to explain dopamine-resistant features of mobility impairments in PD. Recognition of the increased clinical role of cholinergic system degeneration may motivate new research to expand indications for cholinergic therapy in PD.

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“…Although the major pathological hallmarks of PD, Lewy bodies (LB) and Lewy neurites (LN), were originally observed in 1912 [5], α-synuclein (α-syn) was not identified as the major component of these proteinaceous inclusions until 1997 [6] following the discovery of PD kindred with point mutations in the α-syn gene ( SNCA ) [7]. In addition to PD, the presence of α-syn pathological inclusions is one of the defining features of several other neurodegenerative diseases, including dementia with Lewy bodies (DLB), LB variant of Alzheimer’s disease and multiple system atrophy (MSA) [6,8–13].…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of α-synuclein neurodegeneration

Waxman

Giasson²

2009

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

189

187

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α-Synuclein is an abundant highly charged protein that is normally predominantly localized around synaptic vesicles in presynatic terminals. Although the function of this protein is still ill-defined, genetic studies have demonstrated that point mutations or genetic alteration (duplications or triplications) that increase the number of copies of the α-synuclein (SCNA) gene can cause Parkinson’s disease or the related disorder dementia with Lewy bodies. α-Synuclein can aberrantly polymerize into fibrils with typical amyloid properties, and these fibrils are the major component of many types of pathological inclusions, including Lewy bodies, which are associated with neurodegenerative diseases, such as Parkinson’s disease. Genetic studies have clearly established that alteration in the α-synuclein gene can lead to neuronal demise. Although there is substantial evidence supporting the toxic nature of α-synuclein inclusions, other modes of toxicity such as oligomers have been proposed. In this review, some of the evidence for the different mechanisms of α-synuclein toxicity is presented and discussed.

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Fritz Heinrich Lewy (1885–1950)

Cited by 19 publications

References 4 publications

Parkinson’s Disease

Parkinson’s Disease

Cholinergic Dysfunction in Parkinson’s Disease

Molecular mechanisms of α-synuclein neurodegeneration

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