Does altering proteasomal activity and trafficking reduce the arborization mediated specific vulnerability of SNpc dopaminergic neurons of Parkinson’s disease?

Mitochondria are organelles responsible for bioenergetic metabolism, calcium homeostasis, and signal transmission essential for neurons due to their high energy consumption. Accumulating evidence has demonstrated that mitochondria play a key role in axon degeneration and regeneration under physiological and pathological conditions. Mitochondrial dysfunction occurs at an early stage of axon degeneration and involves oxidative stress, energy deficiency, imbalance of mitochondrial dynamics, defects in mitochondrial transport, and mitophagy dysregulation. The restoration of these defective mitochondria by enhancing mitochondrial transport, clearance of reactive oxidative species (ROS), and improving bioenergetic can greatly contribute to axon regeneration. In this paper, we focus on the biological behavior of axonal mitochondria in aging, injury (e.g., traumatic brain and spinal cord injury), and neurodegenerative diseases (Alzheimer's disease, AD; Parkinson's disease, PD; Amyotrophic lateral sclerosis, ALS) and consider the role of mitochondria in axon regeneration. We also compare the behavior of mitochondria in different diseases and outline novel therapeutic strategies for addressing abnormal mitochondrial biological behavior to promote axonal regeneration in neurological diseases and injuries.

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“…Highly branched axons needs increased energy to deal with protein delivery, oxidative stress and mitochondrial dysfunction (Bhaskar et al, 2020).…”

Section: Parkinson's Diseasementioning

confidence: 99%

Mitochondrial Behavior in Axon Degeneration and Regeneration

Wang

Huang

Shang

et al. 2021

Front. Aging Neurosci.

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“…However, the main reason for the specificity of Mn for the SNc dopaminergic neurons is related to the dopamine transporter (DAT); it has been reported that Mn arrives in the neurons via DAT [70][71][72][73]; DAT is related to the MPTP [74], and 6-OHDA neurotoxicity [75], where SNc is more vulnerable than other dopaminergic areas, such as the ventral tegmental area (VTA). It seems that the VTA and SNc dopaminergic cells exhibit topography, biochemistry, and susceptibility to pathological processes differences [76]; the middle and medial SNc express higher levels of DAT than the VTA [74,77]; thus, Mn possibly get SNc dopaminergic cells through the greater amounts of DAT reported on DOI: http://dx.doi.org/10.5772/intechopen.108268 those neurons. Moreover, in PD, the most vulnerable neurons are the SNc dopaminergic ones and not those of the VTA [76,77].…”

Section: Tyrosine Hydroxylase Immunocytochemistrymentioning

confidence: 99%

“…It seems that the VTA and SNc dopaminergic cells exhibit topography, biochemistry, and susceptibility to pathological processes differences [76]; the middle and medial SNc express higher levels of DAT than the VTA [74,77]; thus, Mn possibly get SNc dopaminergic cells through the greater amounts of DAT reported on DOI: http://dx.doi.org/10.5772/intechopen.108268 those neurons. Moreover, in PD, the most vulnerable neurons are the SNc dopaminergic ones and not those of the VTA [76,77].…”

Section: Tyrosine Hydroxylase Immunocytochemistrymentioning

confidence: 99%

Behavioral and Cytological Differences between Two Parkinson’s Disease Experimental Models

Avila-Costa¹,

Ordóñez-Librado²,

Gutiérrez-Valdez³

et al. 2023

Parkinson’s Disease - Animal Models, Current Therapies and Clinical Trials

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The knowledge about the biochemical and behavioral changes in humans with PD has allowed proposing animal models for its study; however, the results obtained so far have been heterogeneous. Recently, we established a novel PD model in rodents by manganese chloride (MnCl2) and manganese acetate (Mn (OAc)3) mixture inhalation. After inhaling, the rodents presented bilateral loss of SNc dopaminergic neurons. Later, we conclude that the alterations are of dopamine origin since L-DOPA reverted the alterations. After six months, SNc significantly reduced the number of cells, and striatal dopamine content decreased by 71%. The animals had postural instability, action tremor, and akinesia; these symptoms improved with L-DOPA, providing evidence that Mn mixture inhalation induces comparable alterations that those in PD patients. Thus, this study aimed to compare the alterations in two different PD experimental models: 6-OHDA unilateral lesion and Mn mixture inhalation through open field test, rotarod performance and the number of SNc dopaminergic neurons. The results show that the Mn-exposed animals have motor alterations and bilateral and progressive SNc neurons degeneration; in contrast, in the 6-OHDA model, the neuronal loss is unilateral and acute, demonstrating that the Mn exposure model better recreates the characteristics observed in PD patients.

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Functional foods and Parkinson's disease: A focus on omega-3 fatty acids

Li,

Song

2024

Functional Foods and Chronic Disease

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Does altering proteasomal activity and trafficking reduce the arborization mediated specific vulnerability of SNpc dopaminergic neurons of Parkinson’s disease?

Cited by 4 publications

References 76 publications

Mitochondrial Behavior in Axon Degeneration and Regeneration

Mitochondrial Behavior in Axon Degeneration and Regeneration

Behavioral and Cytological Differences between Two Parkinson’s Disease Experimental Models

Functional foods and Parkinson's disease: A focus on omega-3 fatty acids

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