A role for viral infections in Parkinson’s etiology?

Olsen, Laura; Dowd, Eilís; McKernan, Declan P.

doi:10.1042/ns20170166

Cited by 42 publications

(35 citation statements)

References 184 publications

(227 reference statements)

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“…In PD, healthy α-synuclein proteins may get misfolded because of mitochondrial dysfunction or oxidative stress or both, which in turn leads to formation of aggregates and Lewy bodies (LBs) (Gundersen, 2010). In the recent years, it has been claimed that a viral (Olsen et al, 2018), neurotoxic (Goldman, 2014) or prion-like infection (Olanow and Brundin, 2013;Matheoud et al, 2019) could be a cause of PD pathogenesis (Hawkes et al, 2007). There exist evidences supporting the Braak hypothesis of LBs (Braak et al, 2004), which suggests that the pathology (misfolded α-synuclein protein) spreads from peripheral regions of the nervous system to the central nervous system through transsynaptic transmission in PD (Braak et al, 2004;Chauhan and Jeans, 2015;Brundin et al, 2016;Brundin and Melki, 2017;Borghammer, 2018).…”

Section: Is Protein Aggregation a Results Or The Cause Of Oxidative Smentioning

confidence: 99%

Neurodegenerative Diseases – Is Metabolic Deficiency the Root Cause?

et al. 2020

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Neurodegenerative diseases, including Alzheimer, Parkinson, Huntington, and amyotrophic lateral sclerosis, are a prominent class of neurological diseases currently without a cure. They are characterized by an inexorable loss of a specific type of neurons. The selective vulnerability of specific neuronal clusters (typically a subcortical cluster) in the early stages, followed by the spread of the disease to higher cortical areas, is a typical pattern of disease progression. Neurodegenerative diseases share a range of molecular and cellular pathologies, including protein aggregation, mitochondrial dysfunction, glutamate toxicity, calcium load, proteolytic stress, oxidative stress, neuroinflammation, and aging, which contribute to neuronal death. Efforts to treat these diseases are often limited by the fact that they tend to address any one of the above pathological changes while ignoring others. Lack of clarity regarding a possible root cause that underlies all the above pathologies poses a significant challenge. In search of an integrative theory for neurodegenerative pathology, we hypothesize that metabolic deficiency in certain vulnerable neuronal clusters is the common underlying thread that links many dimensions of the disease. The current review aims to present an outline of such an integrative theory. We present a new perspective of neurodegenerative diseases as metabolic disorders at molecular, cellular, and systems levels. This helps to understand a common underlying mechanism of the many facets of the disease and may lead to more promising disease-modifying therapeutic interventions. Here, we briefly discuss the selective metabolic vulnerability of specific neuronal clusters and also the involvement of glia and vascular dysfunctions. Any failure in satisfaction of the metabolic demand by the neurons triggers a chain of events that precipitate various manifestations of neurodegenerative pathology.

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Section: Is Protein Aggregation a Results Or The Cause Of Oxidative Smentioning

confidence: 99%

Neurodegenerative Diseases – Is Metabolic Deficiency the Root Cause?

et al. 2020

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“…Neurotropic viruses may negatively impact the normal physiological activity of the CNS by affecting the integrity of the cerebral tissue due to cellular destruction as a result of lytic infection; thus, they can be considered risk factors for developing an alternate neuroimmune response and neurodegenerative diseases such as Parkinson's and Alzheimer diseases (Ringheim and Conant, 2004;Itzhaki, 2018;Olsen et al, 2018). Further, a chronic immune activation may lead to neuroinflammation and subsequently to neurodegeneration.…”

Section: Klks Associated To Viral Infections That Can Affect the Cnsmentioning

confidence: 99%

Involvement of Kallikrein-Related Peptidases in Nervous System Disorders

Mella

Figueroa

Otth

et al. 2020

Front. Cell. Neurosci.

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Kallikrein-related peptidases (KLKs) are a family of serine proteases that when dysregulated may contribute to neuroinflammation and neurodegeneration. In the present review article, we describe what is known about their physiological and pathological roles with an emphasis on KLK6 and KLK8, two KLKs that are highly expressed in the adult central nervous system (CNS). Altered expression and activity of KLK6 have been linked to brain physiology and the development of multiple sclerosis. On the other hand, altered levels of KLK6 in the brain and serum of people affected by Alzheimer's disease and Parkinson's disease have been documented, pointing out to its function in amyloid metabolism and development of synucleinopathies. People who have structural genetic variants of KLK8 can suffer mental illnesses such as intellectual and learning disabilities, seizures, and autism. Increased expression of KLK8 has also been implicated in schizophrenia, bipolar disorder, and depression. Also, we discuss the possible link that exists between KLKs activity and certain viral infections that can affect the nervous system. Although little is known about the exact mechanisms that mediate KLKs function and their participation in neuroinflammatory and neurodegenerative disorders will open a new field to develop novel therapies to modulate their levels and/or activity and their harmful effects on the CNS.

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“…Regarding viral infection, several suggestions have been put forward in the literature, related to viruses with certain brain tropism (see review Olsen, Dowd, & McKernan, ). Virus‐induced models of PD have been reported for the following infection with influenza A virus (Takahashi et al., ) and Japanese encephalitis virus (Ogata, Tashiro, Nukuzuma, Nagashima, & Hall, ).…”

Section: Infections As Putative Players In the Risk Of Developing Parmentioning

confidence: 99%

Immune system responses in Parkinson's disease: Early and dynamic

Tansey

Romero‐Ramos

2018

Eur J of Neuroscience

120

127

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The neuropathological hallmarks of Parkinson's disease (PD) are the degeneration and death of dopamine‐producing neurons in the ventral midbrain, the widespread intraneuronal aggregation of alpha‐synuclein (α) in Lewy bodies and neurites, neuroinflammation, and gliosis. Signs of microglia activation in the PD brain postmortem as well as during disease development revealed by neuroimaging, implicate immune responses in the pathophysiology of the disease. Intensive research during the last two decades has advanced our understanding of the role of these responses in the disease process, yet many questions remain unanswered. A transformative finding in the field has been the confirmation that in vivo microglia are able to respond directly to pathological a‐syn aggregates but also to neuronal dysfunction due to intraneuronal a‐syn toxicity well in advance of neuronal death. In addition, clinical research and disease models have revealed the involvement of both the innate and adaptive immune systems. Indeed, the data suggest that PD leads not only to a microglia response, but also to a cellular and humoral peripheral immune response. Together, these findings compel us to consider a more holistic view of the immunological processes associated with the disease. Central and peripheral immune responses aimed at maintaining neuronal health will ultimately have consequences on neuronal survival. We will review here the most significant findings that have contributed to the current understanding of the immune response in PD, which is proposed to occur early, involve peripheral and brain immune cells, evolve as neuronal dysfunction progresses, and is likely to influence disease progression.

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A role for viral infections in Parkinson’s etiology?

Cited by 42 publications

References 184 publications

Neurodegenerative Diseases – Is Metabolic Deficiency the Root Cause?

Neurodegenerative Diseases – Is Metabolic Deficiency the Root Cause?

Involvement of Kallikrein-Related Peptidases in Nervous System Disorders

Immune system responses in Parkinson's disease: Early and dynamic

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