Cognitive and Physical Intervention in Metals’ Dysfunction and Neurodegeneration

Abstract

Metals—especially iron, copper and manganese—are important elements of brain functions and development. Metal-dysregulation homeostasis is associated with brain-structure damage to the motor, cognitive and emotional systems, and leads to neurodegenerative processes. There is more and more evidence that specialized cognitive and motor exercises can enhance brain function and attenuate neurodegeneration in mechanisms, such as improving neuroplasticity by altering the synaptic structure and function in many brain regions. Psychological and physical methods of rehabilitation are now becoming increasingly important, as pharmacological treatments for movement, cognitive and emotional symptoms are limited. The present study describes physical and cognitive rehabilitation methods of patients associated with metal-induced neurotoxicity such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease and Wilson’s disease. In our review, we describe physical (e.g., virtual-reality environments, robotic-assists training) and psychological (cognitive training, cognitive stimulation, neuropsychological rehabilitation and cognitive-behavioral and mindfulness-based therapies) methods, significantly improving the quality of life and independence of patients associated with storage diseases. Storage diseases are a diverse group of hereditary metabolic defects characterized by the abnormal cumulation of storage material in cells. This topic is being addressed due to the fact that rehabilitation plays a vital role in the treatment of neurodegenerative diseases. Unfortunately so far there are no specific guidelines concerning physiotherapy in neurodegenerative disorders, especially in regards to duration of exercise, type of exercise and intensity, as well as frequency of exercise. This is in part due to the variety of symptoms of these diseases and the various levels of disease progression. This further proves the need for more research to be carried out on the role of exercise in neurodegenerative disorder treatment.

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

“…SMD can be caused by genes not encoding proteins for OXPHOS or mitochondrial functions, secondary to other illnesses (such as cancer, sepsis, and infections, as well as metabolic, neuromuscular, neurodegenerative, and psychiatric diseases); by drugs such as tetracycline and valproate; by environmental factors (including alcohol, cigarette smoke, carbon monoxide, asbestos, and metals, as well as antiretroviral, tetracycline, valproate, and aminoglycosides therapy); or by normal aging [ 163 , 164 , 165 ]. Therefore, SMD can be inherited or acquired.…”

Potential Diets to Improve Mitochondrial Activity in Amyotrophic Lateral Sclerosis

“…With no current cure for the disease, ALS therapeutics seem to have been placed around attempts to slow the progression of the disease and provide symptomatic treatments to maintain patient quality of life (QOL). Therapeutic exercise and/or rehabilitation are also recommended for patients to slow symptomatic progression [ 87 ]. Furthermore, multidisciplinary therapy teams are known to improve patient QOL and have the potential to prolong patient survival [ 88 ].…”

Iron homeostasis imbalance and ferroptosis in brain diseases

“…Iron accumulation in the brain has been reported to be closely related to a variety of neurological conditions in middle‐aged and elderly people, such as stroke, Alzheimer's disease (AD), and Parkinson's disease (PD). Local or extensive brain iron accumulation was found to affect the progression of these diseases, impairing the cognitive and motor ability of patients 6 . In addition, iron accumulation triggers ferroptosis, which is a newly discovered iron‐dependent regulated cell death and different from autophagy, apoptosis, necroptosis, and other forms of cell death.…”

“…Local or extensive brain iron accumulation was found to affect the progression of these diseases, impairing the cognitive and motor ability of patients. 6 In addition, iron accumulation triggers ferroptosis, which is a newly discovered iron‐dependent regulated cell death and different from autophagy, apoptosis, necroptosis, and other forms of cell death. The most essential biochemical attributes of ferroptosis are iron overload and the lethal accumulation of ROS and lipid peroxides accompanied by glutathione (GSH) depletion, glutathione peroxidase (GPX) 4 inactivation within the cell, leading to fatal damage and disorganization of the cell membrane at last.…”