bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2022‒12‒18
five papers selected by
Mikaila Chetty
Goa University

  1. Front Aging Neurosci. 2022 ;14 1006089
      In this review, the relationship between bioenergetics, mitochondrial dysfunction, and inflammation will be and how they contribute to neurodegeneration, specifically in Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) will be reviewed. Long-term changes in mitochondrial function, autophagy dysfunction, and immune activation are commonalities shared across these age-related disorders. Genetic risk factors for these diseases support an autophagy-immune connection in the underlying pathophysiology. Critical areas of deeper evaluation in these bioenergetic processes may lead to potential therapeutics with efficacy across multiple neurodegenerative diseases.
    Keywords:  Alzheimer’s disease; amyotrophic lateral sclerosis; bioenergetics; immune; inflammation; metabolic; multiple sclerosis
  2. Nutrients. 2022 Nov 30. pii: 5086. [Epub ahead of print]14(23):
      Dietary interventions can ameliorate age-related neurological decline. Decades of research of in vitro studies, animal models, and clinical trials support their ability and efficacy to improve behavioral outcomes by inducing biochemical and physiological changes that lead to a more resilient brain. Dietary interventions including calorie restriction, alternate day fasting, time restricted feeding, and fasting mimicking diets not only improve normal brain aging but also slow down, or even reverse, the progression of neurological diseases. In this review, we focus on the effects of intermittent and periodic fasting on improving phenotypic outcomes, such as cognitive and motor-coordination decline, in the normal aging brain through an increase in neurogenesis and synaptic plasticity, and decrease in neuroinflammation, mitochondrial dysfunction, and oxidative stress. We summarize the results of various dietary interventions in animal models of age-related neurological diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, and Multiple Sclerosis and discuss the results of clinical trials that explore the feasibility of dietary interventions in the prevention and treatment of these diseases.
    Keywords:  Alzheimer’s; Parkinson’s; aging; brain; epilepsy; intermittent fasting; multiple sclerosis; neurological diseases; periodic fasting
  3. J Adv Res. 2022 Dec 07. pii: S2090-1232(22)00267-3. [Epub ahead of print]
      BACKGROUND: The gut microbiota (GM) and brain are strongly associated, which significantly affects neuronal development and disorders. GM-derived metabolites modulate neuronal function and influence many cascades in age-related neurodegenerative disorders (NDDs). Because of the dual role of GM in neuroprotection and neurodegeneration, understanding the balance between beneficial and harmful bacteria is crucial for applying this approach to clinical therapies.AIM: of the review This review briefly discusses the role of the gut-brain relationship in promoting brain and cognitive function. Although a healthy gut environment is helpful for brain function, gut dysbiosis can disrupt the brain's environment and create a vicious cycle of degenerative cascades. The ways in which the GM population can affect brain function and the development of neurodegeneration are also discussed. In the treatment and management of NDDs, the beneficial effects of methods targeting GM populations and their derivatives, including probiotics, prebiotics, and fecal microbial transplantation (FMT) are also highlighted. Key scientific concept of the review In this review, we aimed to provide a deeper understanding of the mechanisms of the gut microbe-brain relationship and their twin roles in neurodegeneration progression and therapeutic applications. Here, we attempted to highlight the different pathways connecting the brain and gut, together with the role of GM in neuroprotection and neuronal development. Furthermore, potential roles of GM metabolites in the pathogenesis of brain disorders and in strategies for its treatment are also investigated. By analyzing existing in vitro and clinical studies, this review attempts to identify new and promising therapeutic strategies for central nervous system (CNS) disorders. As the connection between the gut microbe-brain relationship and responses to NDD treatments is less studied, this review will provide new insights into the global mechanisms of GM modulation in disease progression, and identify potential future perspectives for developing new therapies to treat NDDs.
    Keywords:  Gut microbiota; Neurodegeneration; Neurogenesis; Neuroprotection
  4. J Appl Physiol (1985). 2022 Dec 15.
      Healthy brain activity requires precise ion and energy management creating a strong reliance on mitochondrial function. Age-related neurodegeneration leads to a decline in mitochondrial function and increased oxidative stress, with associated declines in mitochondrial mass, respiration capacity, and respiration efficiency. The interdependent processes of mitochondrial protein turnover and mitochondrial dynamics, known together as mitochondrial remodeling, play essential roles in mitochondrial health and therefore brain function. This mini-review describes the role of mitochondria in neurodegeneration and brain health, current practices for assessing both aspects of mitochondrial remodeling, and how exercise mitigates the adverse effects of aging in the brain. Exercise training elicits functional adaptations to improve brain health, and current literature strongly suggests that mitochondrial remodeling plays a vital role in these positive adaptations. Despite substantial implications that the two aspects of mitochondrial remodeling are interdependent, very few investigations have simultaneously measured mitochondrial dynamics and protein synthesis. An improved understanding of the partnership between mitochondrial protein turnover and mitochondrial dynamics will provide a better understanding of their role in both brain health and disease, as well as how they induce protection following exercise.
    Keywords:  brain; exercise; mitochondria; mitochondria remodeling; neurodegeneration
  5. J Clin Med. 2022 Nov 25. pii: 6964. [Epub ahead of print]11(23):
      The glymphatic system is a unique pathway that utilises end-feet Aquaporin 4 (AQP4) channels within perivascular astrocytes, which is believed to cause cerebrospinal fluid (CSF) inflow into perivascular space (PVS), providing nutrients and waste disposal of the brain parenchyma. It is theorised that the bulk flow of CSF within the PVS removes waste products, soluble proteins, and products of metabolic activity, such as amyloid-β (Aβ). In the experimental model, the glymphatic system is selectively active during slow-wave sleep, and its activity is affected by both sleep dysfunction and deprivation. Dysfunction of the glymphatic system has been proposed as a potential key driver of neurodegeneration. This hypothesis is indirectly supported by the close relationship between neurodegenerative diseases and sleep alterations, frequently occurring years before the clinical diagnosis. Therefore, a detailed characterisation of the function of the glymphatic system in human physiology and disease would shed light on its early stage pathophysiology. The study of the glymphatic system is also critical to identifying means for its pharmacological modulation, which may have the potential for disease modification. This review will critically outline the primary evidence from literature about the dysfunction of the glymphatic system in neurodegeneration and discuss the rationale and current knowledge about pharmacological modulation of the glymphatic system in the animal model and its potential clinical applications in human clinical trials.
    Keywords:  APQ4; Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; glymphatics system; idiopathic normal pressure hydrocephalus; motor neurone disease; multiple sclerosis; neurodegeneration; pharmacological modulation