Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of α-synulcein, with an emphasis on Parkinson's disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of calpain. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases.

Lithium has recently been suggested to have neuroprotective effects in several models of neurodegenerative disease including Parkinson's disease (PD). Levodopa (L-Dopa) replacement therapy remains the most common and effective treatment for PD, although it induces the complication of L-Dopa induced dyskinesia after years of use. Here we examined the potential use of lithium in combination with L-Dopa/Carbidopa for both reducing MPTP-induced abnormal involuntary movements (AIMs) as well as protecting against cell death in MPTP-lesioned mice. Chronic lithium administration (0.127% LiCl in the feed) in the presence of daily L-Dopa/ Carbidopa injection for a period of 2 months was sufficient to effectively reduce MPTP-induced AIMs in mice. Mechanistically, lithium was found to suppress MPTP-induced calpain activities in vivo coinciding with down-regulation of calpain-1 but not calpain-2 expression in both the striatum (ST) and the brain stem (BS). Calpain inhibition has previously been associated with increased levels of the rate-limiting enzyme in dopamine synthesis, tyrosine hydroxylase (TH), which is probably mediated by the up-regulation of the transcription factors MEF-2A and 2D. Lithium was found to induce up-regulation of TH expression in the ST and the BS, as well as in N27 rat dopaminergic cells. Further, histone acetyltransferase (HAT) expression was substantially up-regulated by lithium treatment in vitro. These results suggest the potential use of lithium in combination with L-Dopa/Carbidopa not only as a neuroprotectant, but also for reducing AIMs and possibly alleviating potential side-effects associated with the current treatment for PD.

Known genetic mutations and familial hereditary factors account for less than 20-25% of breast cancer cases in women, therefore, most instances have been classified as sporadic cases of unknown aetiologies. Single nucleotide polymorphisms (SNPs) were considered as breast cancer risk factors, but numerous studies have failed to support this assertion. Recent evidence correlates aberrant epigenetic mechanisms in the development and metastatic progression of breast cancer, yet there has been limited progress made to identify the primary aetiology underlying sporadic cases of breast cancer. This has led some researchers to consider alternative hypotheses including in utero exposure to deleterious chemical agents during early development, the immortal strand and the strand-specific imprinting and selective chromatid segregation hypotheses. Here, we integrate prominent alternate models to help guide future research on this very important topic concerning human health. The aetiology of cancer, including breast cancer, is often discussed in the context of genetic and environmental risk factors. Skin cancer is the major class of cancer that occurs both in men and women and its risk factor is predominantly considered to be environmental exposure to sun. On the other hand, genetic risk factors are considered key to the development of breast cancer, the second most common cancer, accounting for nearly one in three cases diagnosed in United States women [1]. The American Cancer Society lists some of the perils in breast cancer as non-modifiable, such as gender (women account for ~99% of the cases), race (Caucasian women have the highest risk), early menses (increased risk if menses begin <12 years age), and increased risk with age. Others are modifiable factors-use of oral contraceptives, hormone replacement therapy, obesity, and use of alcohol-all of which contribute to increased risk of breast cancer. Even though BRCA1 and BRCA2 account for the majority of genetic mutations found in breast cancer cases, only 5-10% of breast cancer cases result directly from specific gene mutations. Another 15-20% of cases are considered to be familial, such that a cluster of cancers affects first-or second-degree relatives, but with an unclear inheritance pattern [2]. The majority of breast cancer cases are termed "sporadic" cancers, with apparently no known cause; however researchers have suggested numerous possibilities over the past several decades. Here we provide an overview of the progression of ideas proposed for explaining the cause of breast cancer, followed by our perspective aimed at suggesting an aetiology that integrates some of the more plausible concepts.According to the American Society of Clinical Oncology, autosomal dominant mutations of the BRCA1 and BRCA2 genes with low penetrance act as predisposing factors for hereditary breast/ovarian cancer (HBOC); that is, not all subjects carrying disease susceptibility mutations even in homozygous conditions develop disease. These mutations are also associated with an inc...