Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. Mitochondria are critical regulators of cell death, a key feature of neurodegeneration. Mutations in mitochondrial DNA and oxidative stress both contribute to ageing, which is the greatest risk factor for neurodegenerative diseases. In all major examples of these diseases there is strong evidence that mitochondrial dysfunction occurs early and acts causally in disease pathogenesis. Moreover, an impressive number of disease-specific proteins interact with mitochondria. Thus, therapies targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria, hold great promise.

Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases

The causes of Parkinson's disease (PD), the second most common neurodegenerative disorder, are still largely unknown. Current thinking is that major gene mutations cause only a small proportion of all cases and that in most cases, non-genetic factors play a part, probably in interaction with susceptibility genes. Numerous epidemiological studies have been done to identify such non-genetic risk factors, but most were small and methodologically limited. Larger, well-designed prospective cohort studies have only recently reached a stage at which they have enough incident patients and person-years of follow-up to investigate possible risk factors and their interactions. In this article, we review what is known about the prevalence, incidence, risk factors, and prognosis of PD from epidemiological studies.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474442206704719.pdf

Epidemiology of Parkinson's disease

Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the agerelated diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.

/pdf/a-mitochondrial-paradigm-of-metabolic-and-degenerative-32cv8y7bvd.pdf

A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and prion diseases are increasingly being realized to have common cellular and molecular mechanisms including protein aggregation and inclusion body formation. The aggregates usually consist of fibers containing misfolded protein with a beta-sheet conformation, termed amyloid. There is partial but not perfect overlap among the cells in which abnormal proteins are deposited and the cells that degenerate. The most likely explanation is that inclusions and other visible protein aggregates represent an end stage of a molecular cascade of several steps, and that earlier steps in the cascade may be more directly tied to pathogenesis than the inclusions themselves. For several diseases, genetic variants assist in explaining the pathogenesis of the more common sporadic forms and developing mouse and other models. There is now increased understanding of the pathways involved in protein aggregation, and some recent clues have emerged as to the molecular mechanisms of cellular toxicity. These are leading to approaches toward rational therapeutics.

/pdf/protein-aggregation-and-neurodegenerative-disease-31sv3urk8w.pdf

Protein aggregation and neurodegenerative disease.

Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6) Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6 We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress These data provide a direct molecular link between mitochondria and the pathogenesis of PD

https://science.sciencemag.org/content/sci/304/5674/1158.full.pdf

Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1

Eating an appropriate food volume, maintaining the required calorie count, and making good nutritional choices are key factors for reducing the risk of obesity, which has many consequences such as Osteoarthritis (OA) that affects the patient’s knee. In this paper, we present a wearable sensor in the form of a necklace embedded with a piezoelectric sensor, that detects skin movement from the lower trachea while eating. In contrast to the previous state-of-the-art piezoelectric sensor-based system that used spectral features, our system fully exploits temporal amplitude-varying signals for optimal features, and thus classifies foods more accurately. Through evaluation of the frame length and the position of swallowing in the frame, we found the best performance was with a frame length of 30 samples (1.5 s), with swallowing located towards the end of the frame. This demonstrates that the chewing sequence carries important information for classification. Additionally, we present a new approach in which the weight of solid food can be estimated from the swallow count, and the calorie count of food can be calculated from their estimated weight. Our system based on a smartphone app helps users live healthily by providing them with real-time feedback about their ingested food types, volume, and calorie count.

/pdf/smart-piezoelectric-based-wearable-system-for-calorie-intake-117rixg6.pdf

Smart Piezoelectric-Based Wearable System for Calorie Intake Estimation Using Machine Learning

Arsenic has been a matter of concern and a major risk factor for public health in many parts of the world. Globally, human health and ecosystems are negatively impacted by arsenicosis of groundwater caused by natural and anthropogenic sources. Inorganic arsenic specifically in its trivalent form is highly neurotoxic due to its ability to cross the blood-brain barrier. Moreover, its exposure poses a significant threat to human health, including CNS alterations and deficits of recent memory, learn 

Zeeshan Ali

Papers

Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1

Smart Piezoelectric-Based Wearable System for Calorie Intake Estimation Using Machine Learning

Acute Exposure to Arsenic Affects Cognition in Drosophila melanogaster Larvae

A Review on the Effect of Nutrition on Exercise-Induced Muscle Damage (EIMD)