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Mitochondrial fission-fusion and trafficking are altered in the fatal neurodegenerative disorder Huntington's disease. Huntingtin is now shown to function directly in these processes by binding the mitochondrial fission factor dynamin- [...]

In the version of this article initially published, the authors omitted to mention that L. Scorrano and colleagues had previously shown increased Drpl activity and mitochondrial fission in cellular models [...]

In the version of this article initially published, the first author of the primary paper that the N&V referred to was incorrectly cited as Petrilli. The correct first author is [...]

The NF-E2-related factor-2 (Nrf2)/antioxidant response element (ARE) signaling pathway regulates phase 2 detoxification genes, including a variety of antioxidative enzymes. We tested neuroprotective effects of the synthetic triterpenoid CDDO-MA, a potent activator of the Nrf2/ARE signaling. CDDO-MA treatment of neuroblastoma SH-SY5Y cells resulted in Nrf2 upregulation and translocation from cytosol to nucleus and subsequent activation of ARE pathway genes. CDDO-MA blocked t-butylhydroperoxide-induced production of reactive oxygen species (ROS) by activation of ARE genes only in wild type, but not Nrf2 knockout mouse embryonic fibroblasts. Oral administration of CDDO-MA resulted in significant protection against MPTP-induced nigrostriatal dopaminergic neurodegeneration, pathological alpha-synuclein accumulation and oxidative damage in mice. Additionally, CDDO-MA treatment in rats produced significant rescue against striatal lesions caused by the neurotoxin 3-NP, and associated increases in the oxidative damage markers malondialdehyde, F2-Isoprostanes, 8-hydroxy-2- deoxyguanosine, 3-nitrotyrosine, and impaired glutathione homeostasis. Our results indicate that the CDDO-MA renders its neuroprotective effects through its potent activation of the Nrf2/ARE pathway, and suggest that triterpenoids may be beneficial for the treatment of neurodegenerative diseases like Parkinson's disease and Huntington's disease. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are characterized by selective and progressive degeneration of neuronal population in the brain, and associated behavioural, motor, psychiatric and cognitive impairments. Aggregation of pathogenic proteins, mitochondrial dysfunction, oxidative stress, transcriptional dysfunction and apoptosis play an important role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease and Amyotrophic lateral sclerosis. Therefore, novel therapies that target each of these mechanisms may be effective in abating the symptoms and slow down the onset and progression of neurodegenerative disorders. This review offers insights into the tremendous utility and versatility of peptides such as neurotrophins, neurotrophic factors (NGF, BDNF and GDNF), neuropeptides, mitochondrial targeted antioxidants/peptides, MitoQ, neurturin, and β-sheet breaker peptides to address the mechanisms and pathogenesis associated with neurodegenerative disorders.

Parkinson's disease is the second most common neurodegenerative disorder characterized by persistent loss of dopaminergic neurons in the SN and clinically associated with cognitive, behavioral and motor deficits. There is an enormous amount of data that provides convincing evidence about the prime involvement of mitochondria in the onset and progression of neurodegeneration. Several studies have also emphasized that accumulation of toxic protein and their aggregates in mitochondria lead to energy deficits, excessive ROS generation, mutations in mitochondrial genome and proteins regulating mitochondrial homeostasis, and impaired mitochondrial dynamics in animal models of PD and patients. Here we discuss about the bioenergetic agents, which have been tested for reducing the mitochondrial dysfunction and associated disease pathology in cellular and animal models of PD and PD patients with encouraging outcomes. We also provide a succinct overview of current therapeutic implications of PGC-1α, SIRT, AMPK, and Nrf2-ARE as salutary targets to overcome the deleterious effects posed by mitochondrial dysfunction in the onset and progression of PD.