Mitochondrial dysfunction in Parkinson’s disease: a possible target for neuroprotection

Gleave, Jacqueline A.; Perri, Peter D.; Nash, Joanne E.

doi:10.1007/s11515-014-1337-8

Cited by 3 publications

(6 citation statements)

References 164 publications

(249 reference statements)

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“…These results suggest that pharmacological inhibition of SIRT2 may have a beneficial, neuroprotective effect in PD. The mitochondrial sirtuins (SIRT3-5) exhibit neuroprotective effect in PD mainly by regulation of the mitochondrial respiratory chain and preservation of mitochondrial antioxidant capacity, as well as promotion of autophagy [ 93 , 94 ]. Expression of SIRT6 is increased in PD and associated with production and secretion of proinflammatory cytokines (e.g., TNF-a) [ 95 ].…”

Section: Sirts In Cns Diseasesmentioning

confidence: 99%

Role of Sirtuins in Physiology and Diseases of the Central Nervous System

et al. 2022

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Silent information regulators, sirtuins (SIRTs), are a family of enzymes which take part in major posttranslational modifications of proteins and contribute to multiple cellular processes, including metabolic and energetic transformations, as well as regulation of the cell cycle. Recently, SIRTs have gained increased attention as the object of research because of their multidirectional activity and possible role in the complex pathomechanisms underlying human diseases. The aim of this study was to review a current literature evidence of SIRTs’ role in the physiology and pathology of the central nervous system (CNS). SIRTs have been demonstrated to be crucial players in the crosstalk between neuroinflammation, neurodegeneration, and metabolic alterations. The elucidation of SIRTs’ role in the background of various CNS diseases offers a chance to define relevant markers of their progression and promising candidates for novel therapeutic targets. Possible diagnostic and therapeutic implications from SIRTs-related investigations are discussed, as well as their future directions and associated challenges.

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Section: Sirts In Cns Diseasesmentioning

confidence: 99%

Role of Sirtuins in Physiology and Diseases of the Central Nervous System

et al. 2022

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“…Hence, experiments have been carried out by overexpressing PGC-1α in vitro and it has shown to protect cells by increasing the levels of antioxidants. In vivo, it protects DA neurons by inhibiting mitochondrial dysfunction. , …”

Section: Novel Therapeutic Strategies To Treat Parkinson’s Diseasementioning

confidence: 99%

“…Mutation in mtDNA has been found to be involved in PD pathogenesis. Currently, limited supportive data is available but it canprove to be a future potential target for PD. , …”

Section: Novel Therapeutic Strategies To Treat Parkinson’s Diseasementioning

confidence: 99%

“…In vivo, it protects DA neurons by inhibiting mitochondrial dysfunction. 87,88 Nuclear receptor-related 1 (Nurr1), is a nuclear receptor involved in both the biosynthesis of dopamine and the survival of DA neurons. 89 Nurr1 has been shown to enhance in vitro and in vivo transcription of TH which is the rate-limiting enzyme of dopamine biosynthesis, and of GTP cyclohydrolase I (GCH1), the first enzyme in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for TH activity.…”

Section: Novel Therapeutic Strategies To Treat Parkinson's Diseasementioning

confidence: 99%

“…Currently, limited supportive data is available but it canprove to be a future potential target for PD. 87,106 4.3. Strategy for Neuronal Regeneration.…”

Section: Novel Therapeutic Strategies To Treat Parkinson's Diseasementioning

confidence: 99%

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Novel Targets for Parkinson’s Disease: Addressing Different Therapeutic Paradigms and Conundrums

Rane

Sarmah

Bhute

et al. 2018

ACS Chem. Neurosci.

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Parkinson's disease (PD) is a neurodegenerative disease that is pathologically characterized by degeneration of dopamine neurons in the substantia nigra pars compacta (SNpc). PD leads to clinical motor features that include rigidity, tremor, and bradykinesia. Despite multiple available therapies for PD, the clinical features continue to progress, and patients suffer progressive disability. Many advances have been made in PD therapy which directly target the cause of the disease rather than providing symptomatic relief. A neuroprotective or disease modifying strategy that can slow or cease clinical progression and worsening disability remains as a major unmet medical need for PD management. The present review discusses potential novel therapies for PD that include recent interventions in the form of immunomodulatory techniques and stem cell therapy. Further, an introspective approach to identify numerous other novel targets that can alleviate PD pathogenesis and enable physicians to practice multitargeted therapy and that may provide a ray of hope to PD patients in the future are discussed.

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Neuroprotective effects of GLP-1 class drugs in Parkinson’s disease

Lv,

Feng,

Guan

et al. 2024

Front. Neurol.

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Parkinson’s disease (PD) is a chronic, progressive neurological disorder primarily affecting motor control, clinically characterized by resting tremor, bradykinesia, rigidity, and other symptoms that significantly diminish the quality of life. Currently, available treatments only alleviate symptoms without halting or delaying disease progression. There is a significant association between PD and type 2 diabetes mellitus (T2DM), possibly due to shared pathological mechanisms such as insulin resistance, chronic inflammation, and mitochondrial dysfunction. PD is caused by a deficiency of dopamine, a neurotransmitter in the brain that plays a critical role in the control of movement. Glucose metabolism and energy metabolism disorders also play an important role in the pathogenesis of PD. This review investigates the neuroprotective mechanisms of glucagon-like peptide-1 (GLP-1) and its receptor agonists, offering novel insights into potential therapeutic strategies for PD. GLP-1 class drugs, primarily used in diabetes management, show promise in addressing PD’s underlying pathophysiological mechanisms, including energy metabolism and neuroprotection. These drugs can cross the blood–brain barrier, improve insulin resistance, stabilize mitochondrial function, and enhance neuronal survival and function. Additionally, they exhibit significant anti-inflammatory and antioxidative stress effects, which are crucial in neurodegenerative diseases like PD. Research indicates that GLP-1 receptor agonists could improve both motor and cognitive symptoms in PD patients, marking a potential breakthrough in PD treatment and prevention. Further exploration of GLP-1’s molecular mechanisms in PD could provide new preventive and therapeutic approaches, especially for PD patients with concurrent T2DM. By targeting both metabolic and neurodegenerative pathways, GLP-1 receptor agonists represent a multifaceted approach to PD treatment, offering hope for better disease management and improved patient outcomes.

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Mitochondrial dysfunction in Parkinson’s disease: a possible target for neuroprotection

Abstract: Mitochondria are dynamic organelles which are required for maintaining cellular homeostasis.

Cited by 3 publications

References 164 publications

Role of Sirtuins in Physiology and Diseases of the Central Nervous System

Role of Sirtuins in Physiology and Diseases of the Central Nervous System

Novel Targets for Parkinson’s Disease: Addressing Different Therapeutic Paradigms and Conundrums

Neuroprotective effects of GLP-1 class drugs in Parkinson’s disease

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