Degeneration process of Lewy bodies in the brains of patients with dementia with Lewy bodies using α-synuclein-immunohistochemistry

Iseki, Eizo; Marui, Wami; Akiyama, Haruhiko; Uéda, Kenji; Kosaka, Kenji

doi:10.1016/s0304-3940(00)01090-9

Cited by 54 publications

(40 citation statements)

References 18 publications

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“…2H) but have not so far been described in cases of aFTLD-U, NIFID, BIBD and FALS with FUS mutations. They may represent a residual form of inclusions after neuronal death, similar to the ghost tangles in Alzheimer's disease or the extracellular Lewy bodies in dementia with Lewy bodies [35]. It could be important to clarify whether they are specific for a subset of FALS with BI cases or whether they are commonly found in other disorders with FUS accumulation.…”

Section: Discussionmentioning

confidence: 99%

Occurrence of basophilic inclusions and FUS-immunoreactive neuronal and glial inclusions in a case of familial amyotrophic lateral sclerosis

Kobayashi

Tsuchiya

Arai

et al. 2010

Journal of the Neurological Sciences

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Section: Discussionmentioning

confidence: 99%

Occurrence of basophilic inclusions and FUS-immunoreactive neuronal and glial inclusions in a case of familial amyotrophic lateral sclerosis

Kobayashi

Tsuchiya

Arai

et al. 2010

Journal of the Neurological Sciences

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“…Moreover, another study found that intracellular Lewy bodies were positive for complement proteins C3d and C4d, suggesting an activation of the classical complement pathway in Lewy bodies-bearing neurons, inducing microglial activation and neuronal death [118]. Finally, Zhang et al [119] recently showed, using primary rat and mouse midbrain cultures, that both soluble oligomeric forms and aggregated α-synuclein, can activate microglia and led to enhanced dopaminergic neurotoxicity induced by aggregated or soluble oligomeric forms of α-synuclein.…”

Section: How Are Microglial Cells Activated In Pd?mentioning

confidence: 98%

An Inflammatory Pathomechanism for Parkinsons Disease?

Wersinger

Sidhu²

2006

CMC

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Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), striatal dopamine deficiency and appearance of Lewy bodies. Inflammatory and immune, or even autoimmune, stigmata, have been described in post-mortem brains of PD patients. Although disputed in humans, a reactive astrocytosis and a lymphocytic infiltration in the SNpc have been observed in animal models of PD, which need further examination. This review summarizes the current knowledge on brain inflammation in humans with PD, and how inflammation and/or (auto)immune reactions within the SNpc could be linked to other pathophysiological mechanisms that have been hypothesized for the etiology of PD, such as oxidative stress, exposure to neurotoxins, and post-infectious or post-traumatic injuries. In particular, we discuss how microglial cells could be activated during the course of PD, and present a new hypothesis that PD-linked protein (alpha-synuclein, in particular) aggregates could be implicated in their activation, to induce a chronic and sustained inflammation involved in the progression, at least, of the disease. The current status of anti-inflammatory agents, either already tried in PD clinical trials or putatively usefull as adjuvant therapies for PD, is also discussed.

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“…Immune and inflammatory responses in the CNS are also observed in other chronic and acute neurological conditions, including multiple sclerosis, myasthenia gravis, head trauma and stroke, as well as in animal models of some of these disorders (3,7,56,57). Complement activation proteins have been also demonstrated in association with Lewy and Pick bodies in Parkinson and Pick's disease, respectively (58,59), with dystrophic neurites and early stage extracellular neurofibrillary tangles in the Parkinsonism dementia complex of Guam (60), with clusters of degenerating axons in amyotrophic lateral sclerosis (61) as well as around immunoglobulin light chain (AL) and transthyretin (TTR) amyloid deposits in peripheral nerves in both acquired and hereditary neuropathy (51,62). In Creutzfeldt-Jacob and Gerstmann-Straussler-Scheinker diseases (63), complement activation products have been found associated with amyloid plaques, and it has been recently demonstrated that the complement system plays a role in the early prion pathogenesis in transmissible spongiform encephalopathies (64,65).…”

Section: Discussionmentioning

confidence: 98%

Complement Activation in Chromosome 13 Dementias

Rostagno¹,

Révész²,

Lashley³

et al. 2002

Journal of Biological Chemistry

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Hemolytic experiments and enzyme-linked immunosorbent assays specific for the activation products iC3b, C4d, Bb, and C5b-9 indicated that ABri and ADan are able to fully activate the complement cascade at levels comparable to those generated by A␤1-42. ABri and ADan specifically bound C1q with high affinity and formed stable complexes in physiological conditions. Activation proceeds ϳ70 -75% through the classical pathway while only ϳ25-30% seems to occur through the alternative pathway. The data suggest that the chronic inflammatory response generated by the amyloid peptides in vivo might be a contributing factor for the pathogenesis of FBD and FDD and, in more general terms, to other neurodegenerative conditions.The classic hallmark lesions of Alzheimer's disease (AD), 1 cerebral senile plaques and neurofibrillary tangles (NFTs), have been known for nearly a century. During the past two decades, a wide range of inflammatory markers, typically absent or significantly reduced in the normal elderly population, were reported in AD brains (1), and accumulating evidence suggests that sustained brain inflammation might be an essential cofactor in AD pathogenesis (2, 3). In this sense, immunological factors and inflammation mediators, including complement proteins and pro-inflammatory peptides generated at different stages of complement activation (4) as well as various cytokines (5), have been implicated in accelerating the progression of AD.The complement system is a highly regulated, powerful effector mechanism of the immune system that destroys and clears deleterious substances. It is composed of more than twenty proteins that become sequentially activated in a proteolytic cascade. Originally, activation of the complement system was thought to occur only by binding of immune complexes to C1q, the recognition component of the classical pathway. However, it became then evident that the complement system can directly be activated, in the absence of antibody, by interaction of certain foreign molecules with C3 (alternative activation pathway), C1q (antibody-independent classical activation pathway), or by specific lectins on the surface of certain microorganisms (lectin activation pathway) (3,6,7).The first step in the classical complement pathway involves the binding of an activator to C1q resulting in the subsequent conversion of the serine proesterases C1r and C1s to their active forms and, in turn, in the activation of C4, C2, and then C3. The alternative pathway differs from the classic pathway in that activation begins at the level of C3 and involves factors B and D and Properdin. Proteolytic modification of C3 by either pathway leads to the cleavage of C5 and the incorporation of C6, C7, C8, and multiple molecules of C9 resulting in the formation of the membrane attack complex (MAC), C5b-9, a transmembrane channel capable to produce cell lysis (8).Activation-derived proteins of both the classical and alternative pathways have been demonstrated in association with AD lesions by numerous groups (3). We investigate...

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Degeneration process of Lewy bodies in the brains of patients with dementia with Lewy bodies using α-synuclein-immunohistochemistry

Cited by 54 publications

References 18 publications

Occurrence of basophilic inclusions and FUS-immunoreactive neuronal and glial inclusions in a case of familial amyotrophic lateral sclerosis

Occurrence of basophilic inclusions and FUS-immunoreactive neuronal and glial inclusions in a case of familial amyotrophic lateral sclerosis

An Inflammatory Pathomechanism for Parkinsons Disease?

Complement Activation in Chromosome 13 Dementias

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