Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson’s Disease
Parkinson’s disease (PD) is a chronic and progressive age-related neurodegenerative disease affecting up to 3% of the global population over 65 years of age. Currently, the underlying physiological aetiology of PD is unknown. However, the diagnosed disorder shares many common non-motor symptoms asso...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/5/1117 |
| _version_ | 1797601237782233088 |
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| author | Shane Michael Ravenhill Andrew Howard Evans Sheila Gillard Crewther |
| author_facet | Shane Michael Ravenhill Andrew Howard Evans Sheila Gillard Crewther |
| author_sort | Shane Michael Ravenhill |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a chronic and progressive age-related neurodegenerative disease affecting up to 3% of the global population over 65 years of age. Currently, the underlying physiological aetiology of PD is unknown. However, the diagnosed disorder shares many common non-motor symptoms associated with ageing-related neurodegenerative disease progression, such as neuroinflammation, microglial activation, neuronal mitochondrial impairment, and chronic autonomic nervous system dysfunction. Clinical PD has been linked to many interrelated biological and molecular processes, such as escalating proinflammatory immune responses, mitochondrial impairment, lower adenosine triphosphate (ATP) availability, increasing release of neurotoxic reactive oxygen species (ROS), impaired blood brain barrier integrity, chronic activation of microglia, and damage to dopaminergic neurons consistently associated with motor and cognitive decline. Prodromal PD has also been associated with orthostatic hypotension and many other age-related impairments, such as sleep disruption, impaired gut microbiome, and constipation. Thus, this review aimed to present evidence linking mitochondrial dysfunction, including elevated oxidative stress, ROS, and impaired cellular energy production, with the overactivation and escalation of a microglial-mediated proinflammatory immune response as naturally occurring and damaging interlinked bidirectional and self-perpetuating cycles that share common pathological processes in ageing and PD. We propose that both chronic inflammation, microglial activation, and neuronal mitochondrial impairment should be considered as concurrently influencing each other along a continuum rather than as separate and isolated linear metabolic events that affect specific aspects of neural processing and brain function. |
| first_indexed | 2024-03-11T03:59:18Z |
| format | Article |
| id | doaj.art-16a849a4e76947a4bd6a254994feef60 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T03:59:18Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-16a849a4e76947a4bd6a254994feef602023-11-18T00:15:51ZengMDPI AGAntioxidants2076-39212023-05-01125111710.3390/antiox12051117Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson’s DiseaseShane Michael Ravenhill0Andrew Howard Evans1Sheila Gillard Crewther2School of Psychology and Public Health, La Trobe University, Bundoora 3083, AustraliaDepartment of Medicine, The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, AustraliaSchool of Psychology and Public Health, La Trobe University, Bundoora 3083, AustraliaParkinson’s disease (PD) is a chronic and progressive age-related neurodegenerative disease affecting up to 3% of the global population over 65 years of age. Currently, the underlying physiological aetiology of PD is unknown. However, the diagnosed disorder shares many common non-motor symptoms associated with ageing-related neurodegenerative disease progression, such as neuroinflammation, microglial activation, neuronal mitochondrial impairment, and chronic autonomic nervous system dysfunction. Clinical PD has been linked to many interrelated biological and molecular processes, such as escalating proinflammatory immune responses, mitochondrial impairment, lower adenosine triphosphate (ATP) availability, increasing release of neurotoxic reactive oxygen species (ROS), impaired blood brain barrier integrity, chronic activation of microglia, and damage to dopaminergic neurons consistently associated with motor and cognitive decline. Prodromal PD has also been associated with orthostatic hypotension and many other age-related impairments, such as sleep disruption, impaired gut microbiome, and constipation. Thus, this review aimed to present evidence linking mitochondrial dysfunction, including elevated oxidative stress, ROS, and impaired cellular energy production, with the overactivation and escalation of a microglial-mediated proinflammatory immune response as naturally occurring and damaging interlinked bidirectional and self-perpetuating cycles that share common pathological processes in ageing and PD. We propose that both chronic inflammation, microglial activation, and neuronal mitochondrial impairment should be considered as concurrently influencing each other along a continuum rather than as separate and isolated linear metabolic events that affect specific aspects of neural processing and brain function.https://www.mdpi.com/2076-3921/12/5/1117alpha-synucleinadenosine triphosphatebioenergetic capacitycytokinesdopamine neuronshomeostasis |
| spellingShingle | Shane Michael Ravenhill Andrew Howard Evans Sheila Gillard Crewther Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson’s Disease Antioxidants alpha-synuclein adenosine triphosphate bioenergetic capacity cytokines dopamine neurons homeostasis |
| title | Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson’s Disease |
| title_full | Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson’s Disease |
| title_fullStr | Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson’s Disease |
| title_full_unstemmed | Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson’s Disease |
| title_short | Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson’s Disease |
| title_sort | escalating bi directional feedback loops between proinflammatory microglia and mitochondria in ageing and post diagnosis of parkinson s disease |
| topic | alpha-synuclein adenosine triphosphate bioenergetic capacity cytokines dopamine neurons homeostasis |
| url | https://www.mdpi.com/2076-3921/12/5/1117 |
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